About FANCA
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
FANCA c.2003G>T, p.(Ser668Ile)
Classification
Uncertain significance
Variant description:
No variant summary was recorded for this case.
Five-step scale from benign to pathogenic. This variant is uncertain. Select a step to read what it means.
Uncertain.The recorded classification is uncertain significance.
In plain language
Gene-level background from the recorded interpretation.
Words with a dotted underline have a short definition. Hover or tap them.
LYFE Sciences is an AI system, and it can make mistakes.
Criteria may be applied incorrectly, sources may be misread, and a
confident-looking classification can still be wrong.
Double-check every criterion and its underlying evidence
before relying on any call.
01The reasoning
How it was classified
The recorded framework is Not recorded. The criteria and strengths shown below come from the saved assessment; this page does not recalculate the classification.
Recorded applied criteria
The applied criteria and their strengths are shown as assessed under the stated framework.
Pathogenic evidence criteria: 1
Benign evidence criteria: 1
Pathogenic criteria applied · 1
PM2Moderate
PM2 · moderate
NM_000135.3:c.2003G>T is extremely rare in population databases. In gnomAD v2.1 exomes, the variant is observed at an allele frequency of 6.42×10⁻⁶ (1/155,698 alleles; MAF 0.00064%), far below the 0.1% threshold for PM2. In gnomAD v4.1, the AF is 3.22×10⁻⁶ (5/1,550,610 alleles; MAF 0.00032%). No homozygotes are reported in either dataset. The variant is absent from gnomAD-Canada. This ultra-rare population frequency supports a moderate evidence weight for pathogenicity under the ACMG/AMP framework.
Benign criteria applied · 1
BP4Supporting
BP4 · supporting
Multiple lines of computational evidence suggest NM_000135.3:c.2003G>T (p.Ser668Ile) has no deleterious impact. REVEL predicts a benign score of 0.276 (well below the 0.5 threshold commonly used for pathogenic prediction). BayesDel predicts a benign score of -0.261 (negative scores indicate benign). SpliceAI predicts no splicing alteration (max delta score = 0.00). The concordance of multiple in silico predictors supports a supporting benign evidence weight.
Recorded classification: Uncertain significance
gene-specific framework lacked a usable explicit final combination framework, so generic ACMG/AMP 2015 final-combination rules were applied as fallback; applied criteria: PM2 moderate, BP4 supporting benign; combination = 1 moderate + 1 supporting benign, which maps to VUS.
02The sources
Evidence at a glance
Evidence summaries and captured source records, where available. Missing entries should not be interpreted as negative findings.
gnomAD v4.1
gnomAD v2.1
Population frequency
5 / 1,550,610 alleles
gnomAD v4.1: 5 / 1,550,610 alleles. Recorded AF 3.22454e-06. Recorded homozygote count 0.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 6.42269e-06; MAF= 0.00064%, 1/155698 alleles, homozygotes = 0) and has highest observed frequency in the East Asian population (AF= 8.8433e-05; MAF= 0.00884%, 1/11308 alleles, homozygotes = 0).
gnomAD-Canada
Not available in gnomAD-Canada v1.0.
SpliceAI score
0.000 maximum delta
Recorded SpliceAI maximum delta score: 0.000. Refer to the recorded PP3/BP4 rationale for interpretation.
ClinVar submissions
4 reported laboratory submissions
4 Uncertain significance. ClinVar API review status: criteria provided, multiple submitters, no conflicts.
Context only
ClinVar ↗
Functional evidence
Statement recorded
OncoKB did not identify variant-specific reviewed functional evidence for this variant; gene-level curated context is available for reviewer follow-up. FANCA, a DNA repair protein, is infrequently altered in cancer.
No listed criterion applied
OncoKB ↗
COSMIC
Cancer Hotspots
Somatic evidence
No matching record reported
This variant has not previously been reported in somatic cancers (COSMIC).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.
Context only
For specialists
Technical detail
ACMG/AMP criteria under Not recorded, with the data and sources behind each one.
29 criteria with recorded statuses: 2 met · 22 not met · 0 not assessed · 5 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
Met
Not met
Not assessed
Not applicable
NM_000135.3:c.2003G>T (p.Ser668Ile) is a missense variant in FANCA, a gene associated with autosomal recessive Fanconi anemia. The variant is extremely rare in population databases with an allele frequency of 6.42×10⁻⁶ in gnomAD v2.1 and 3.22×10⁻⁶ in gnomAD v4.1, meeting PM2 (moderate).
Multiple in silico tools predict a benign effect: REVEL score 0.276, BayesDel score -0.261, and SpliceAI max delta 0.00, meeting BP4 (supporting benign).
The variant is classified as Uncertain significance in ClinVar (VCID 2161267) by four clinical laboratories with criteria provided but no expert panel review. No pathogenic assertion from a reputable source exists.
No functional studies, case-control data, segregation data, de novo observations, or variant-specific literature citations were identified for this variant. OncoKB reports Unknown Oncogenic Effect with no curated PMIDs.
The only applicable evidence criteria are PM2 (moderate, supporting pathogenicity) and BP4 (supporting benign). These offset each other, leaving the variant with no net evidence weight toward either pathogenic or benign classification. The variant remains a Variant of Uncertain Significance.
No criteria match.
Met · 2
PM2 ModerateNM_000135.3:c.2003G>T is extremely rare in population databases. In gnomAD v2.1 exomes, the variant is observed at an allele frequency of 6.42×10⁻⁶ (1/155,698 alleles; MAF 0.00064%), far below the 0.1% threshold for PM2. In gnomAD v4.1, the AF is 3.22×10⁻⁶ (5/1,550,610 alleles; MAF 0.00032%). No homozygotes are reported in either dataset. The variant is absent from gnomAD-Canada. This ultra-rare population frequency supports a moderate evidence weight for pathogenicity under the ACMG/AMP framework. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1: AF=6.42e-06 (1/155
- 698 alleles)
- 0 homozygotes
- gnomAD v4.1: AF=3.22e-06 (5/1
- 550
- 610 alleles)
- grpmax FAF=8.1e-06
- gnomAD-Canada v1.0: variant not present
Sources
BP4 SupportingMultiple lines of computational evidence suggest NM_000135.3:c.2003G>T (p.Ser668Ile) has no deleterious impact. REVEL predicts a benign score of 0.276 (well below the 0.5 threshold commonly used for pathogenic prediction). BayesDel predicts a benign score of -0.261 (negative scores indicate benign). SpliceAI predicts no splicing alteration (max delta score = 0.00). The concordance of multiple in silico predictors supports a supporting benign evidence weight. Details ▾Hide ▴
Evidence considered
- REVEL score: 0.276 (benign
- below 0.5)
- BayesDel score: -0.261 (benign
- negative)
- SpliceAI max delta: 0.00 (no splicing impact predicted)
Sources
Not met · 22 · evaluated, threshold not reached
PS1 No evidence of a previously established pathogenic missense variant at the same amino acid position (Ser668) producing the same amino acid change (Ser668Ile) was identified in ClinVar, the literature, or any other source reviewed. Details ▾Hide ▴
Evidence considered
- ClinVar does not list a different pathogenic missense variant at residue 668 with a Ser668Ile change
- PM5 candidate search yielded no same-residue pathogenic comparators
Still missing
- Comprehensive literature search for Ser668 missense variants not performed beyond automated pipeline sources
Sources
clinvar ↗pm5_candidates
PS2 No de novo data are available for NM_000135.3:c.2003G>T in any source reviewed. No publication, ClinVar submission, or database entry reports a confirmed de novo occurrence of this variant. Details ▾Hide ▴
PS3 No functional experimental data were identified for NM_000135.3:c.2003G>T (p.Ser668Ile). OncoKB reports Unknown Oncogenic Effect with no associated PMIDs. None of the publications reviewed contain variant-specific functional assays. No systematic range characterization (tiling screen, saturation mutagenesis, truncation series) spanning residue 668 was identified. Details ▾Hide ▴
Evidence considered
- OncoKB classifies this variant as Unknown Oncogenic Effect with no curated functional PMIDs
- No functional studies identified in the literature pass or any full-text paper reviewed
Still missing
- Functional characterization of p.Ser668Ile would require targeted experimental studies (e.g.
- FANCA complementation assay
- FA pathway activation readout)
Sources
PS4 No case-control studies or case series demonstrating enrichment of NM_000135.3:c.2003G>T in affected individuals over controls were identified. The variant has not been reported in COSMIC (somatic cancers). ClinVar submissions are limited to clinical laboratory classifications of Uncertain significance without associated case-level phenotype data. Details ▾Hide ▴
Evidence considered
- ClinVar contains 4 clinical laboratory submissions
- all classifying as Uncertain significance
- COSMIC reports no somatic occurrences
- No case counts or affected individual tallies available
Still missing
- No published case series or patient cohorts with this variant were identified
Sources
PM1 The variant does not lie in a statistically significant mutational hotspot as assessed by cancerhotspots.org (residue_significant=false). Residue 668 is not within a well-characterized functional domain with domain-specific evidence for PM1 in the materials reviewed. No domain-level functional characterization spanning residue 668 was identified in the literature. Details ▾Hide ▴
Evidence considered
- cancerhotspots.org does not report residue 668 as a significant hotspot
- No domain-level functional evidence for the region containing Ser668 in the reviewed literature
Still missing
- Domain-level functional characterization of the FANCA C-terminal region may exist in literature not captured by the triage pipeline
PM5 No pathogenic missense variant at the same amino acid residue (Ser668) with a different amino acid change was identified as a comparator. The automatic PM5 candidate harvest found no same-residue pathogenic variants in ClinVar. PM5 cannot be applied without a confirmed pathogenic comparator at the same residue. Details ▾Hide ▴
Evidence considered
- PM5 candidate collection found 0 same-residue pathogenic comparator variants
- ClinVar search did not identify a different pathogenic missense at residue 668
Still missing
- Manual ClinVar search for any pathogenic missense at residue 668 in FANCA would be needed to definitively rule out PM5
Sources
pm5_candidatesclinvar ↗
PM6 No de novo occurrence of NM_000135.3:c.2003G>T has been reported with confirmed maternity and paternity. No publication or ClinVar submission describes this variant as a de novo event. PM6 cannot be applied without a documented de novo case. Details ▾Hide ▴
Evidence considered
- No de novo report identified in ClinVar or associated literature
Still missing
- De novo case data would require clinical testing reports or published trio analyses not available
Sources
PP1 No segregation data are available for NM_000135.3:c.2003G>T. No publication or database record describes co-segregation of this variant with disease in a family. PP1 cannot be applied without segregation evidence. Details ▾Hide ▴
Evidence considered
- No segregation data identified in any source reviewed
Still missing
- Segregation analysis would require family-based genetic testing data not present in the case folder
PP2 PP2 requires a low rate of benign missense variation in the gene and demonstration that missense variants are a common disease mechanism. While FANCA missense variants can be pathogenic in Fanconi anemia, no gene-level missense constraint metric (e.g., gnomAD missense Z-score, missense o/e ratio) was available in the evidence materials to confirm a low rate of benign missense variation specifically for FANCA. PP2 cannot be applied without this quantitative constraint data. Details ▾Hide ▴
Evidence considered
- FANCA is associated with Fanconi anemia
- and missense variants are a recognized disease mechanism
- No gnomAD gene-level missense constraint score (Z-score or o/e) was available in the case materials
Still missing
- gnomAD gene constraint metrics (missense Z-score
- o/e ratio) for FANCA are not present in the evidence packet
Sources
PP3 Multiple lines of in silico computational evidence do not support a deleterious effect of this variant. REVEL predicts a benign score of 0.276 (below the 0.5 threshold). BayesDel predicts a benign score of -0.261 (negative scores indicate benign). SpliceAI predicts no splicing impact (max delta score = 0.00). The computational evidence consistently points toward a benign or tolerated substitution, so PP3 is not met. Details ▾Hide ▴
Evidence considered
- REVEL score: 0.276 (benign range
- below 0.5)
- BayesDel score: -0.261 (negative
- consistent with benign)
- SpliceAI max delta: 0.00 (no predicted splice impact)
Sources
PP4 No patient phenotype or clinical data specific to NM_000135.3:c.2003G>T are available. The ClinVar submissions list no specific condition labels or clinical features. No publication describes the phenotype of individuals carrying this variant. PP4 requires patient phenotype specificity, which cannot be assessed without clinical data. Details ▾Hide ▴
Evidence considered
- ClinVar submissions contain no condition labels or phenotype descriptions for this variant
Still missing
- Patient phenotype data are not available in any reviewed source
Sources
PP5 No reputable source has classified NM_000135.3:c.2003G>T as pathogenic. ClinVar reports Uncertain significance from 4 clinical laboratories. The ClinVar-associated PMIDs triaged for PP5 (20301575, 24121147, 26389210) are GeneReviews and policy guideline documents that do not mention this specific variant. No expert panel, clinical practice guideline, or well-established clinical laboratory has asserted pathogenicity for this variant. Details ▾Hide ▴
Evidence considered
- ClinVar classification: Uncertain significance (VCID 2161267)
- criteria provided
- single submitter tier
- No expert panel or reputable source asserting pathogenicity
- Literature_pass PP5 candidates (20301575
- 24121147
- 26389210) are general references that do not mention this variant
Sources
BA1 The gnomAD allele frequency of NM_000135.3:c.2003G>T is 6.42×10⁻⁶ (v2.1) and 3.22×10⁻⁶ (v4.1), far below the 1% BA1 threshold. This is an ultra-rare variant, not a common polymorphism, so BA1 (stand-alone benign) does not apply. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1 AF: 0.000064%
- well below 1% BA1 threshold
- gnomAD v4.1 AF: 0.000032%
Sources
BS1 The gnomAD allele frequency (6.42×10⁻⁶) is far below the 0.3% BS1 threshold. The variant is too rare in population databases to support a strong benign classification based on allele frequency. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1 AF: 0.000064%
- well below 0.3% BS1 threshold
- gnomAD v4.1 AF: 0.000032%
Sources
BS2 No data are available regarding observation of NM_000135.3:c.2003G>T in healthy adult individuals. BS2 requires documented observation in trans with a pathogenic variant (for recessive disorders) or in a healthy adult with full penetrance expected at an early age (for dominant disorders). No such evidence exists in the reviewed materials. Details ▾Hide ▴
Evidence considered
- No data on observation in healthy adult controls or in trans with a pathogenic variant
Still missing
- Healthy control cohort data or case-level genotype data are not available
BS3 No functional experimental data exist demonstrating that NM_000135.3:c.2003G>T (p.Ser668Ile) has no deleterious effect on protein function or splicing. No well-established in vitro or in vivo functional studies showing a benign effect were identified. Details ▾Hide ▴
Evidence considered
- No functional studies demonstrating no deleterious effect were identified
- OncoKB reports Unknown Oncogenic Effect with no associated PMIDs
Still missing
- Functional studies evaluating p.Ser668Ile would be needed to support or refute BS3
Sources
BS4 No segregation data are available to assess lack of segregation with disease. BS4 requires observation that the variant does not segregate with the phenotype in affected family members, which cannot be evaluated without family-based genetic data. Details ▾Hide ▴
Evidence considered
- No segregation data available in any reviewed source
Still missing
- Family-based genotype data are not available
BP1 BP1 applies to missense variants in genes where primarily truncating variants cause disease. FANCA is associated with Fanconi anemia, and missense variants are a well-established pathogenic mechanism in this gene. Both truncating and missense pathogenic variants are reported in ClinVar and the literature for FANCA, so the BP1 premise (primarily truncating mechanism) is not satisfied. Details ▾Hide ▴
Evidence considered
- FANCA pathogenic variants include both missense and truncating types
- Missense variants are a recognized disease mechanism for Fanconi anemia
Sources
clinvar ↗pvs1_gene_context
BP2 No data are available regarding observation of NM_000135.3:c.2003G>T in trans with a known pathogenic variant in FANCA (relevant for recessive Fanconi anemia) or in cis with a pathogenic variant. BP2 cannot be applied without genotype phasing data. Details ▾Hide ▴
Evidence considered
- No in-trans or in-cis observation with a pathogenic variant was identified
Still missing
- Phased genotype data are not available
BP5 No case has been identified where NM_000135.3:c.2003G>T is observed in an individual with an alternate molecular basis for disease. BP5 requires a documented case where the variant is present but another pathogenic variant explains the phenotype, and no such evidence exists in the reviewed materials. Details ▾Hide ▴
Evidence considered
- No case with an alternate molecular basis was identified
Still missing
- Case-level molecular data would be needed to assess BP5
BP6 No reputable source has classified NM_000135.3:c.2003G>T as benign. ClinVar classification is Uncertain significance from 4 clinical laboratories. BP6 requires a reputable source (e.g., expert panel, clinical practice guideline) to report the variant as benign, and no such assertion exists. Details ▾Hide ▴
Evidence considered
- ClinVar classification is Uncertain significance (VCID 2161267)
- No expert panel or reputable source asserting benign classification
Sources
PS5 No reputable source (expert panel, clinical practice guideline, or well-established laboratory) has reported NM_000135.3:c.2003G>T as definitively pathogenic. ClinVar classification is Uncertain significance from 4 clinical laboratories with criteria provided but no expert panel review. Details ▾Hide ▴
Evidence considered
- ClinVar classification is Uncertain significance (VCID 2161267)
- criteria provided
- single submitter tier
- No expert panel assertion of pathogenicity
Sources
Not applicable · 5· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/ANM_000135.3:c.2003G>T is a missense variant (p.Ser668Ile). PVS1 is reserved for null variants (nonsense, frameshift, canonical splice ±1/2, initiation codon, single/multi-exon deletion) per the ClinGen SVI PVS1 decision tree (PMC6185798). This variant does not fall into any default null-variant bucket. No functional data exist demonstrating that this specific missense abolishes protein function to a null-equivalent degree. Details ▾Hide ▴
Evidence considered
- Variant is a missense substitution (p.Ser668Ile)
- not a null variant
- pvs1_variant_assessment confirms variant_bucket=other
- apply_generic_pvs1_framework=false
Sources
PM3 N/APM3 applies to recessive disorders when a variant is detected in trans with a known pathogenic variant. No in-trans genotype data are available for this case. Details ▾Hide ▴
No further detail was recorded.
PM4 N/APM4 applies to protein length changes due to in-frame deletions/insertions or stop-loss variants. NM_000135.3:c.2003G>T is a missense substitution, not a protein-length-altering variant. Details ▾Hide ▴
No further detail was recorded.
BP3 N/ABP3 applies to in-frame deletions/insertions in a repetitive region without a known function. NM_000135.3:c.2003G>T is a missense substitution, not an in-frame indel. Details ▾Hide ▴
No further detail was recorded.
BP7 N/ABP7 applies to synonymous (silent) variants and intronic variants outside of conserved splice sites for which splicing prediction algorithms predict no impact. NM_000135.3:c.2003G>T is a missense variant producing p.Ser668Ile, not a synonymous or intronic variant. BP7 is not applicable to missense variants. Details ▾Hide ▴
No further detail was recorded.
Identifiers
- Gene
- FANCA
- Transcript
- NM_000135.3
- Coding (HGVS c.)
- NM_000135.3:c.2003G>T
- Protein (HGVS p.)
- NP_000126.2:p.(Ser668Ile)
- GRCh38
- chr16:89773282 C>A
- GRCh37
- chr16:89839690 C>A
- ClinVar
- 2161267
Gene diagram
Every interpreted variant in FANCA, mapped onto the exon structure of NM_000135.3. Select a row to find it on the plot.
FANCANM_000135.3
Fetching transcript structure from UCSC…
Exons
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Transcript span
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Strand
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Variants mapped
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Source
UCSC ncbiRefSeqCurated
All variants in FANCA
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Select a row to find it on the plot; use the link to open its page.
| Protein | Location | Classification | Link |
|---|
gnomAD v4.1
5 / 1,550,610 alleles
AF 3.22e-06 · 0 homozygotes · FAF 8.1e-06
gnomAD v2.1
1 / 155,698 alleles
AF 6.42e-06 · 0 homozygotes
gnomAD-Canada v1.0
Allele count data not recorded
By genetic ancestry
gnomAD v4.1
AF 3.2e-06 · 5 / 1,550,610 alleles · 0 hom · FAF 8.1e-06
| East Asian2 / 40,926 | 4.9e-05 |
| Remaining individuals1 / 60,076 | 1.7e-05 |
| South Asian1 / 84,044 | 1.2e-05 |
| European (non-Finnish)1 / 1,146,544 | 8.7e-07 |
0 alternate alleles recorded in 6 other groups: Admixed American, European (Finnish), Amish, Middle Eastern, Ashkenazi Jewish, African/African American.
gnomAD v2.1
AF 6.4e-06 · 1 / 155,698 alleles · 0 hom
| East Asian1 / 11,308 | 8.8e-05 |
0 alternate alleles recorded in 7 other groups: African/African American, Admixed American, Ashkenazi Jewish, European (Finnish), European (non-Finnish), Remaining individuals, South Asian.
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 3.22454e-06; MAF= 0.00032%, 5/1550610 alleles, homozygotes = 0) and has highest observed frequency in the East Asian population (AF= 4.88687e-05; MAF= 0.00489%, 2/40926 alleles, homozygotes = 0); grpmax FAF= 8.1e-06.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 6.42269e-06; MAF= 0.00064%, 1/155698 alleles, homozygotes = 0) and has highest observed frequency in the East Asian population (AF= 8.8433e-05; MAF= 0.00884%, 1/11308 alleles, homozygotes = 0).
gnomAD-Canada
Not available in gnomAD-Canada v1.0.
SpliceAI and Pangolin
Other predictors
- REVEL
- 0.276
- BayesDel
- -0.261
How the predictions were used
BP4 SupportingMultiple lines of computational evidence suggest NM_000135.3:c.2003G>T (p.Ser668Ile) has no deleterious impact. REVEL predicts a benign score of 0.276 (well below the 0.5 threshold commonly used for pathogenic prediction). BayesDel predicts a benign score of -0.261 (negative scores indicate benign). SpliceAI predicts no splicing alteration (max delta score = 0.00). The concordance of multiple in silico predictors supports a supporting benign evidence weight. Details ▾Hide ▴
Evidence considered
- REVEL score: 0.276 (benign
- below 0.5)
- BayesDel score: -0.261 (benign
- negative)
- SpliceAI max delta: 0.00 (no splicing impact predicted)
Sources
PP3 Multiple lines of in silico computational evidence do not support a deleterious effect of this variant. REVEL predicts a benign score of 0.276 (below the 0.5 threshold). BayesDel predicts a benign score of -0.261 (negative scores indicate benign). SpliceAI predicts no splicing impact (max delta score = 0.00). The computational evidence consistently points toward a benign or tolerated substitution, so PP3 is not met. Details ▾Hide ▴
Evidence considered
- REVEL score: 0.276 (benign range
- below 0.5)
- BayesDel score: -0.261 (negative
- consistent with benign)
- SpliceAI max delta: 0.00 (no predicted splice impact)
Sources
BP7 N/ABP7 applies to synonymous (silent) variants and intronic variants outside of conserved splice sites for which splicing prediction algorithms predict no impact. NM_000135.3:c.2003G>T is a missense variant producing p.Ser668Ile, not a synonymous or intronic variant. BP7 is not applicable to missense variants. Details ▾Hide ▴
No further detail was recorded.
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.276. BayesDel score = -0.261458.
7 paper records listed. No publication is explicitly linked to an applied criterion in the recorded metadata. None of the listed paper records explicitly indicates that the variant is named.
Recorded publications
-
PMID 25730230 ↗Expanded carrier screening in reproductive medicine-points to consider: a joint statement of the American College of Medical Genetics and Genomics, American College of Obstetricians and Gynecologists, National Society of Genetic Counselors, Perinatal Quality Foundation, and Society for Maternal-Fetal Medicine.Edwards JG et al. · 2015Edwards et al. present a joint statement on expanded carrier screening in reproductive medicine from ACMG, ACOG, NSGC, Perinatal Quality Foundation, and SMFM. The paper provides policy guidance on carrier screening panels but does not mention FANCA or NM_000135.3:c.2003G>T.Does not name this variant
-
PMID 25741868 ↗Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.This publication is the ACMG/AMP standards and guidelines for the interpretation of sequence variants. It describes the general classification framework and evidence criteria but does not discuss the specific FANCA variant NM_000135.3:c.2003G>T (p.Ser668Ile).Does not name this variant
-
PMID 26467025 ↗A Standardized DNA Variant Scoring System for Pathogenicity Assessments in Mendelian Disorders.Karbassi et al. describe a standardized rules-based DNA variant scoring system for pathogenicity assessment in Mendelian disorders. The paper reports methodology and aggregate analysis of over 16,500 variant assessments but does not mention the specific FANCA variant NM_000135.3:c.2003G>T (p.Ser668Ile).Does not name this variant
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PMID 20301575 ↗Fanconi Anemia.This is the GeneReviews entry for Fanconi Anemia. It provides comprehensive gene-level and disease-level information about FANCA and the Fanconi anemia pathway but does not mention the specific variant NM_000135.3:c.2003G>T (p.Ser668Ile). No abstract or full text was available in the case folder to confirm variant-level content.Does not name this variant
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PMID 24121147 ↗Appropriateness of newborn screening for α1-antitrypsin deficiency.Teckman J et al. · 2014Teckman et al. discuss the appropriateness of newborn screening for alpha-1-antitrypsin (AAT) deficiency. This paper focuses on SERPINA1 and AAT deficiency screening policy. FANCA and NM_000135.3:c.2003G>T are not discussed.Does not name this variant
-
PMID 26389210 ↗Genetics of Breast and Gynecologic Cancers (PDQ®): Health Professional Version.This is the PDQ Cancer Genetics Editorial Board summary on Genetics of Breast and Gynecologic Cancers. It is a general review of hereditary cancer genes and does not mention the specific FANCA variant NM_000135.3:c.2003G>T (p.Ser668Ile). No abstract or full text was available in the case folder.Does not name this variant
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PMID 24022298 ↗Offering prenatal diagnostic tests: European guidelines for clinical practice [corrected].Skirton H et al. · 2014Skirton et al. present European guidelines for offering prenatal diagnostic tests in clinical practice. The paper discusses prenatal testing policy and does not mention FANCA or the specific variant NM_000135.3:c.2003G>T (p.Ser668Ile).Does not name this variant
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
gnomAD v4.1
5 / 1,550,610 recorded alleles
Open source ↗
gnomAD v2.1
Captured gnomAD v2.1 source record
Open source ↗
SpliceAI Lookup
Recorded maximum delta 0.000
Open source ↗
ClinVar
4 Uncertain significance
Open source ↗
COSMIC
Captured COSMIC source record
Open source ↗
Cancer hotspots
Captured Cancer Hotspots source record
Open source ↗
OncoKB
Captured OncoKB source record
Open source ↗
All source links
- ClinVar ↗www.ncbi.nlm.nih.gov/clinvar/variation/2161267/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/16-89839690-C-A?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr16-89773282-C-A?dataset=gn…
- gnomAD-Canada ↗http://192.168.4.76:8001/variant/16-89773282-C-A
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_000135.3%3Ac.2003…
- OncoKB ↗www.oncokb.org/gene/FANCA/S668I
- COSMIC ↗cancer.sanger.ac.uk/cosmic/search?q=FANCA+c.2003G%3ET
- Cancer hotspots ↗www.cancerhotspots.org/
Statements for reports
The evidence statements recorded by the interpretation pipeline. They have not been reinterpreted by the page.
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 3.22454e-06; MAF= 0.00032%, 5/1550610 alleles, homozygotes = 0) and has highest observed frequency in the East Asian population (AF= 4.88687e-05; MAF= 0.00489%, 2/40926 alleles, homozygotes = 0); grpmax FAF= 8.1e-06.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 6.42269e-06; MAF= 0.00064%, 1/155698 alleles, homozygotes = 0) and has highest observed frequency in the East Asian population (AF= 8.8433e-05; MAF= 0.00884%, 1/11308 alleles, homozygotes = 0).
gnomAD-Canada
Not available in gnomAD-Canada v1.0.
ClinVar
This variant has been reported in ClinVar as Uncertain significance (4 clinical laboratories). (ClinVarID = 2161267)
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.276. BayesDel score = -0.261458.
Functional
OncoKB did not identify variant-specific reviewed functional evidence for this variant; gene-level curated context is available for reviewer follow-up. FANCA, a DNA repair protein, is infrequently altered in cancer.
Somatic
This variant does not lie in a statistically significant hotspot. This variant has not previously been reported in somatic cancers (COSMIC).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.