About FANCL
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
FANCL c.355G>A, p.(Gly119Arg)
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
PM2Supporting
PM2 · supporting
NM_018062.3:c.355G>A is extremely rare in population databases. In gnomAD v2.1, the total allele frequency is 7.96e-06 (2/251,302 alleles; 0.0008%), and in gnomAD v4.1 the allele frequency is 6.21e-07 (1/1,611,258 alleles; 0.00006%). Both are well below the 0.1% PM2 threshold for generic ACMG/AMP. The variant is absent from gnomAD-Canada. The highest subpopulation frequency is in East Asian (v2.1: 0.0109%, 2/18,394).
Benign criteria applied · 1
BP4Supporting
BP4 · supporting
Multiple lines of computational evidence suggest no impact on the gene product. REVEL score is 0.104 (well below typical pathogenic thresholds ≥0.5), BayesDel score is -0.400665 (negative, supporting a benign interpretation), and SpliceAI predicts no splicing impact (max delta score = 0.03, below the 0.1 threshold). Three independent in silico tools concordantly predict a benign or non-deleterious effect.
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 supporting, BP4 supporting benign; combination = 1 supporting + 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
1 / 1,611,258 alleles
gnomAD v4.1: 1 / 1,611,258 alleles. Recorded AF 6.20633e-07. Recorded homozygote count 0.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 7.95855e-06; MAF= 0.00080%, 2/251302 alleles, homozygotes = 0) and has highest observed frequency in the East Asian population (AF= 0.000108731; MAF= 0.01087%, 2/18394 alleles, homozygotes = 0); grpmax FAF= 1.897e-05.
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
SpliceAI score
0.030 maximum delta
Recorded SpliceAI maximum delta score: 0.030. Refer to the recorded PP3/BP4 rationale for interpretation.
ClinVar submissions
2 reported laboratory submissions
2 Uncertain significance.
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. FANCL, an E3 ubiquitin ligase involved in DNA repair, is infrequently altered in cancer. Germline mutations of FANCL are associated with the cancer pr
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.
26 criteria with recorded statuses: 2 met · 21 not met · 0 not assessed · 3 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
Met
Not met
Not assessed
Not applicable
NM_018062.3:c.355G>A (p.Gly119Arg) is a missense variant in exon 5 of FANCL, a gene associated with autosomal recessive Fanconi anemia. PVS1 is not applicable as this is not a null variant.
This variant is extremely rare in population databases, with an allele frequency of 7.96e-06 (0.0008%) in gnomAD v2.1 and 6.21e-07 (0.00006%) in gnomAD v4.1, meeting PM2 at supporting level.
Multiple computational predictors (REVEL 0.104, BayesDel -0.400665, SpliceAI max delta 0.03) concordantly suggest a benign effect, meeting BP4 at supporting level.
The variant has been reported in ClinVar as uncertain significance by two clinical laboratories (ClinVar ID 653483). No pathogenic or benign assertions exist from expert panels.
Functional data, segregation analysis, de novo observations, case-control studies, and variant-specific literature are all absent for this variant. No publications among the seven reviewed mention NM_018062.3:c.355G>A.
The balanced evidence profile (PM2_supporting vs. BP4_supporting) results in a net score of zero, consistent with a classification of uncertain significance under ACMG/AMP 2015 generic rules.
No criteria match.
Met · 2
PM2 SupportingNM_018062.3:c.355G>A is extremely rare in population databases. In gnomAD v2.1, the total allele frequency is 7.96e-06 (2/251,302 alleles; 0.0008%), and in gnomAD v4.1 the allele frequency is 6.21e-07 (1/1,611,258 alleles; 0.00006%). Both are well below the 0.1% PM2 threshold for generic ACMG/AMP. The variant is absent from gnomAD-Canada. The highest subpopulation frequency is in East Asian (v2.1: 0.0109%, 2/18,394). Details ▾Hide ▴
Evidence considered
- gnomAD v2.1: AF=7.96e-06 (2/251
- 302 alleles
- 0 hom)
- grpmax FAF=1.897e-05.
- gnomAD v4.1: AF=6.21e-07 (1/1
- 611
- 258 alleles
- 0 hom).
- gnomAD-Canada: absent.
Sources
BP4 SupportingMultiple lines of computational evidence suggest no impact on the gene product. REVEL score is 0.104 (well below typical pathogenic thresholds ≥0.5), BayesDel score is -0.400665 (negative, supporting a benign interpretation), and SpliceAI predicts no splicing impact (max delta score = 0.03, below the 0.1 threshold). Three independent in silico tools concordantly predict a benign or non-deleterious effect. Details ▾Hide ▴
Evidence considered
- REVEL: 0.104 (not predicted damaging).
- BayesDel: -0.400665 (predicted benign).
- SpliceAI: max delta 0.03 (no predicted splice impact).
Sources
Not met · 21 · evaluated, threshold not reached
PS2 No de novo observation of NM_018062.3:c.355G>A has been reported in any of the seven reviewed publications. No de novo data are present in ClinVar submissions. Details ▾Hide ▴
Evidence considered
- ClinVar submissions (SCV000949413
- SCV005658711) report germline origin but provide no de novo confirmation data.
Still missing
- No de novo testing data available for this variant.
Sources
PS3 No functional studies of NM_018062.3:c.355G>A (p.Gly119Arg) were identified. OncoKB reports Unknown Oncogenic Effect with no variant-specific reviewed functional evidence. None of the seven reviewed publications contain functional data for this variant. Details ▾Hide ▴
Evidence considered
- OncoKB classification: Unknown Oncogenic Effect
- no variant-specific functional studies curated.
Still missing
- No in vitro or in vivo functional characterization of p.Gly119Arg has been performed.
Sources
PS4 No case-control or case-series data for NM_018062.3:c.355G>A have been reported. ClinVar contains two submissions, both classifying the variant as uncertain significance; neither provides affected-vs-control cohort data. The variant's prevalence in gnomAD (2/251,302 in v2.1) does not support a statistically significant enrichment in affected individuals. Details ▾Hide ▴
Evidence considered
- ClinVar: 2 submitters
- both VUS
- gnomAD: 2 alleles in v2.1
- 1 allele in v4.1
- no case-control data.
Still missing
- No case-control or cohort enrichment data available.
Sources
PM1 This variant does not lie in a statistically significant mutational hotspot. The hotspots analysis found no enrichment at residue 119 or the surrounding region. No critical functional domain has been specifically implicated at this residue by the available evidence. Details ▾Hide ▴
Evidence considered
- Cancer Hotspots analysis: residue not significant
- exact variant not listed.
Still missing
- No FANCL-specific domain-level constraint or functional domain mapping available from CSPEC/VCEP.
PM6 No de novo observation of this variant has been reported. Neither ClinVar submissions nor the reviewed publications provide any de novo confirmation data. Details ▾Hide ▴
Evidence considered
- ClinVar submissions lack de novo confirmation
- no publications report de novo occurrence.
Still missing
- No trio or de novo testing data available.
Sources
PP1 No segregation data are available for NM_018062.3:c.355G>A. None of the reviewed publications report familial cosegregation analysis for this variant. Details ▾Hide ▴
Evidence considered
- No segregation data found in any reviewed source.
Still missing
- No family studies or segregation analysis performed.
PP2 FANCL is associated with Fanconi anemia, an autosomal recessive disorder where loss of function is a known disease mechanism. However, there are insufficient data to establish that FANCL has a low rate of benign missense variation and that missense variants are a common mechanism of disease. The HCI prior model does not support FANCL for custom PP2 scoring. Details ▾Hide ▴
Evidence considered
- HCI prior: gene not supported
- no custom PP2 score available.
Still missing
- No gene-specific benign missense constraint metric available.
PP3 Multiple in silico predictors do not support a deleterious effect. REVEL score is 0.104 (below typical pathogenic thresholds of ≥0.5), BayesDel score is -0.400665 (negative, favoring benign), and SpliceAI predicts no splicing impact (max delta score = 0.03). These do not meet the threshold for PP3. Details ▾Hide ▴
Evidence considered
- REVEL: 0.104 (low).
- BayesDel: -0.400665 (benign).
- SpliceAI: max delta 0.03 (no splice impact).
Sources
PP4 No specific phenotypic data are available for individuals harboring NM_018062.3:c.355G>A. None of the reviewed publications describe patients with this variant, and ClinVar submissions do not include condition labels or phenotype details. Details ▾Hide ▴
Evidence considered
- ClinVar submissions lack condition labels
- no publications describe affected carriers.
Still missing
- No phenotype data for variant carriers.
Sources
PP5 No reputable source has recently reported NM_018062.3:c.355G>A as pathogenic. ClinVar classifies it as uncertain significance (two clinical laboratories, criteria provided single submitter). The ClinVar-associated publications are gene-level overviews (GeneReviews, PDQ summaries, practice guidelines) that do not mention this specific variant. Details ▾Hide ▴
Evidence considered
- ClinVar VCV000653483: VUS
- no expert panel or professional society pathogenic assertion.
Sources
BA1 The allele frequency of NM_018062.3:c.355G>A is well below the 1% BA1 threshold. gnomAD v2.1 total AF is 7.96e-06 (0.0008%); gnomAD v4.1 total AF is 6.21e-07 (0.00006%). The variant is too rare to qualify as a common benign polymorphism. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1 AF=7.96e-06 << 1%.
- gnomAD v4.1 AF=6.21e-07 << 1%.
Sources
BS1 The allele frequency is well below the 0.3% BS1 threshold for generic ACMG/AMP. gnomAD v2.1 total AF is 0.0008% and v4.1 AF is 0.00006%. Even the highest subpopulation frequency (East Asian in v2.1: 0.0109%) remains far below 0.3%. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1 total AF=0.0008% << 0.3%.
- East Asian subpop AF=0.0109% << 0.3%.
Sources
BS2 No homozygous observations of this variant have been reported in gnomAD (v2.1: 0 homozygotes out of 251,302; v4.1: 0 homozygotes out of 1,611,258). No case-control data demonstrate presence in healthy controls at a frequency inconsistent with disease penetrance. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1: 0 homozygotes.
- gnomAD v4.1: 0 homozygotes.
- No healthy-control data available.
Still missing
- No data on variant presence in confirmed healthy controls.
Sources
BS3 No functional studies demonstrating a neutral or benign effect of p.Gly119Arg have been identified. While computational predictors favor a benign effect (REVEL 0.104, BayesDel -0.400665), these constitute in silico evidence (BP4) rather than the well-established functional assay data required for BS3. Details ▾Hide ▴
Evidence considered
- No in vitro or in vivo functional assay data for p.Gly119Arg.
Still missing
- No experimental functional characterization of this variant.
Sources
revelbayesdel
BS4 No segregation data are available for NM_018062.3:c.355G>A. Lack of cosegregation with disease cannot be assessed without family studies. Details ▾Hide ▴
Evidence considered
- No segregation or family study data available.
Still missing
- No family-based segregation analysis.
BP1 FANCL is associated with Fanconi anemia, an autosomal recessive disorder where loss of function is a known disease mechanism. However, BP1 requires that a gene be one for which primarily truncating variants cause disease. While LoF is supported in FANCL, missense variants can also be pathogenic in Fanconi anemia genes (as evidenced by known pathogenic missense variants in FANCA, FANCC, FANCG, BRCA2/FANCD1, etc.). There is insufficient evidence to assert that only truncating variants cause FANCL-related disease. Details ▾Hide ▴
Evidence considered
- PVS1 gene context confirms LoF mechanism supported but does not establish that disease is exclusively caused by truncating variants.
Still missing
- No CSPEC/VCEP determination on whether missense variants are a recognized mechanism in FANCL-related Fanconi anemia.
Sources
pvs1_gene_context
BP2 NM_018062.3:c.355G>A has not been observed in trans with a known pathogenic FANCL variant in any reviewed source. No phase information is available from gnomAD, ClinVar, or the reviewed literature. Details ▾Hide ▴
Evidence considered
- No observation in trans with a pathogenic variant reported.
Still missing
- No phasing data available
- no observation with a known pathogenic FANCL variant.
Sources
BP5 No case has been identified in which NM_018062.3:c.355G>A was observed alongside an alternate molecular basis for disease. No such data exist in the reviewed literature or ClinVar submissions. Details ▾Hide ▴
Evidence considered
- No alternate-molecular-basis observation available.
Still missing
- No case with an alternate causative variant identified.
BP6 No reputable source has classified NM_018062.3:c.355G>A as benign or likely benign. ClinVar reports uncertain significance from two clinical laboratories; no benign assertion exists from any expert panel or professional body. Details ▾Hide ▴
Evidence considered
- ClinVar VCV000653483: VUS only
- no benign or likely benign classification.
Sources
BP7 NM_018062.3:c.355G>A is a missense variant (p.Gly119Arg), not a synonymous or intronic variant. BP7 applies only to silent variants at non-conserved nucleotides with no predicted splice impact. This variant changes the amino acid and is therefore ineligible for BP7. Details ▾Hide ▴
Evidence considered
- Missense variant: non-synonymous amino acid change p.Gly119Arg.
PS5 No reputable source has classified NM_018062.3:c.355G>A as pathogenic. ClinVar reports uncertain significance from two clinical laboratories; no expert panel or professional society has asserted a pathogenic classification. Details ▾Hide ▴
Evidence considered
- ClinVar VCV000653483: Uncertain significance
- criteria provided single submitter
- 2 clinical laboratories.
Sources
Not applicable · 3· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/AThis is a missense variant (c.355G>A, p.Gly119Arg) located in exon 5 of FANCL. It does not fall into the PVS1 null-variant categories of nonsense, frameshift, or canonical ±1,2 splice consensus variants per ClinGen SVI PVS1 recommendations (PMC6185798). The generic PVS1 framework does not apply to this variant class. Details ▾Hide ▴
Evidence considered
- Missense substitution in exon 5
- variant_bucket='other'
- apply_generic_pvs1_framework=false per automated assessment.
Sources
pvs1_generic_framework ↗pvs1_variant_assessment
PS1 N/ANo known pathogenic variant at amino acid position 119 with a different amino acid change has been identified in ClinVar, COSMIC, or the reviewed literature. Without a same-residue pathogenic comparator, PS1 cannot be applied. Details ▾Hide ▴
Evidence considered
- ClinVar VCV000653483 lists only this variant as VUS
- PM5 candidate search found zero same-residue candidates.
Sources
clinvar ↗pm5_candidates
PM5 N/AAutomated PM5 candidate search found zero same-residue comparator variants at amino acid position 119 with a different pathogenic missense change. Unable to confirm classic same-residue PM5 semantics. Details ▾Hide ▴
Evidence considered
- PM5 candidate search: pm5_mode=unknown
- eligible_for_classic_pm5_search=false
- 0 candidates.
Sources
pm5_candidates
Identifiers
- Gene
- FANCL
- Transcript
- NM_018062.3
- Coding (HGVS c.)
- NM_018062.3:c.355G>A
- Protein (HGVS p.)
- NP_060532.2:p.(Gly119Arg)
- GRCh38
- chr2:58221961 C>T
- GRCh37
- chr2:58449096 C>T
- ClinVar
- 653483
Gene diagram
Every interpreted variant in FANCL, mapped onto the exon structure of NM_018062.3. Select a row to find it on the plot.
FANCLNM_018062.3
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 FANCL
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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
1 / 1,611,258 alleles
AF 6.21e-07 · 0 homozygotes
gnomAD v2.1
2 / 251,302 alleles
AF 7.96e-06 · 0 homozygotes · FAF 1.9e-05
gnomAD-Canada v1.0
Allele count data not recorded
By genetic ancestry
gnomAD v4.1
AF 6.2e-07 · 1 / 1,611,258 alleles · 0 hom
| East Asian1 / 44,768 | 2.2e-05 |
0 alternate alleles recorded in 9 other groups: Remaining individuals, Admixed American, European (Finnish), Amish, Middle Eastern, South Asian, Ashkenazi Jewish, African/African American, European (non-Finnish).
gnomAD v2.1
AF 8e-06 · 2 / 251,302 alleles · 0 hom · FAF 1.9e-05
| East Asian2 / 18,394 | 0.00011 |
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= 6.20633e-07; MAF= 0.00006%, 1/1611258 alleles, homozygotes = 0) and has highest observed frequency in the East Asian population (AF= 2.23374e-05; MAF= 0.00223%, 1/44768 alleles, homozygotes = 0).
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 7.95855e-06; MAF= 0.00080%, 2/251302 alleles, homozygotes = 0) and has highest observed frequency in the East Asian population (AF= 0.000108731; MAF= 0.01087%, 2/18394 alleles, homozygotes = 0); grpmax FAF= 1.897e-05.
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
SpliceAI and Pangolin
Other predictors
- REVEL
- 0.104
- BayesDel
- -0.401
How the predictions were used
BP4 SupportingMultiple lines of computational evidence suggest no impact on the gene product. REVEL score is 0.104 (well below typical pathogenic thresholds ≥0.5), BayesDel score is -0.400665 (negative, supporting a benign interpretation), and SpliceAI predicts no splicing impact (max delta score = 0.03, below the 0.1 threshold). Three independent in silico tools concordantly predict a benign or non-deleterious effect. Details ▾Hide ▴
Evidence considered
- REVEL: 0.104 (not predicted damaging).
- BayesDel: -0.400665 (predicted benign).
- SpliceAI: max delta 0.03 (no predicted splice impact).
Sources
PP3 Multiple in silico predictors do not support a deleterious effect. REVEL score is 0.104 (below typical pathogenic thresholds of ≥0.5), BayesDel score is -0.400665 (negative, favoring benign), and SpliceAI predicts no splicing impact (max delta score = 0.03). These do not meet the threshold for PP3. Details ▾Hide ▴
Evidence considered
- REVEL: 0.104 (low).
- BayesDel: -0.400665 (benign).
- SpliceAI: max delta 0.03 (no splice impact).
Sources
BP7 NM_018062.3:c.355G>A is a missense variant (p.Gly119Arg), not a synonymous or intronic variant. BP7 applies only to silent variants at non-conserved nucleotides with no predicted splice impact. This variant changes the amino acid and is therefore ineligible for BP7. Details ▾Hide ▴
Evidence considered
- Missense variant: non-synonymous amino acid change p.Gly119Arg.
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.03). REVEL score = 0.104. BayesDel score = -0.400665.
6 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 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.Richards S et al. · 2015This is the joint ACMG/AMP consensus recommendation for sequence variant interpretation. It describes the general classification framework, rules for combining criteria, and standards for evidence weighting. NM_018062.3:c.355G>A is not mentioned.Does not name this variant
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PMID 18197057 ↗Carrier screening in individuals of Ashkenazi Jewish descent.Gross SJ et al. · 2008ACMG practice guideline on carrier screening in individuals of Ashkenazi Jewish descent. Lists disorders and genes recommended for carrier screening in this population. NM_018062.3:c.355G>A is not mentioned in the full text.Does not name this variant
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PMID 20301575 ↗Fanconi Anemia.Adam MP et al. · 1993GeneReviews entry for Fanconi Anemia, providing a comprehensive overview of clinical characteristics, genetic etiology, and management. Discusses FANCL at the gene level as one of over 20 FA complementation groups. NM_018062.3:c.355G>A is not mentioned.Does not name this variant
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PMID 26389210 ↗Genetics of Breast and Gynecologic Cancers (PDQ®): Health Professional Version.PDQ Cancer Genetics Editorial Board · 2002PDQ cancer genetics summary on Genetics of Breast and Gynecologic Cancers. Covers hereditary cancer syndromes and associated genes at a population level. NM_018062.3:c.355G>A is not mentioned.Does not name this variant
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PMID 26389258 ↗Cancer Genetics Risk Assessment and Counseling (PDQ®): Health Professional Version.PDQ Cancer Genetics Editorial Board · 2002PDQ cancer genetics summary on Cancer Genetics Risk Assessment and Counseling. Discusses risk assessment frameworks, genetic counseling principles, and hereditary cancer syndromes. NM_018062.3:c.355G>A is not mentioned.Does not name this variant
-
PMID 26389333 ↗Genetics of Skin Cancer (PDQ®): Health Professional Version.PDQ Cancer Genetics Editorial Board · 2002PDQ cancer genetics summary on Genetics of Skin Cancer. Discusses hereditary skin cancer syndromes and associated genes. NM_018062.3:c.355G>A is not mentioned.Does not name this variant
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
gnomAD v4.1
1 / 1,611,258 recorded alleles
Open source ↗
gnomAD v2.1
Captured gnomAD v2.1 source record
Open source ↗
SpliceAI Lookup
Recorded maximum delta 0.030
Open source ↗
ClinVar
2 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/653483/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/2-58449096-C-T?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr2-58221961-C-T?dataset=gnomad_r4
- gnomAD-Canada ↗http://192.168.4.76:8001/variant/2-58221961-C-T
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_018062.3%3Ac.355G…
- OncoKB ↗www.oncokb.org/gene/FANCL/G119R
- COSMIC ↗cancer.sanger.ac.uk/cosmic/search?q=FANCL+c.355G%3EA
- 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= 6.20633e-07; MAF= 0.00006%, 1/1611258 alleles, homozygotes = 0) and has highest observed frequency in the East Asian population (AF= 2.23374e-05; MAF= 0.00223%, 1/44768 alleles, homozygotes = 0).
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 7.95855e-06; MAF= 0.00080%, 2/251302 alleles, homozygotes = 0) and has highest observed frequency in the East Asian population (AF= 0.000108731; MAF= 0.01087%, 2/18394 alleles, homozygotes = 0); grpmax FAF= 1.897e-05.
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
ClinVar
This variant has been reported in ClinVar as Uncertain significance (2 clinical laboratories). (ClinVarID = 653483)
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.03). REVEL score = 0.104. BayesDel score = -0.400665.
Functional
OncoKB did not identify variant-specific reviewed functional evidence for this variant; gene-level curated context is available for reviewer follow-up. FANCL, an E3 ubiquitin ligase involved in DNA repair, is infrequently altered in cancer. Germline mutations of FANCL are associated with the cancer pr
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.