About FANCL
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
FANCL c.2T>C, p.(Met1?)
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: 2
Benign evidence criteria: 0
Pathogenic criteria applied · 2
PVS1Moderate
PVS1 · moderate
This start-loss variant (c.2T>C, p.Met1?) abolishes the initiation codon of FANCL. Loss of function is an established disease mechanism for FANCL (Fanconi anemia, autosomal recessive). Per ClinGen SVI PVS1 recommendations (PMC6185798), initiation codon variants qualify for PVS1 at moderate strength when no alternative in-frame start codon is present in the same exon. No downstream ATG was identified in FANCL exon 1.
PM2Supporting
PM2 · supporting
This variant is present at very low frequency in population databases: gnomAD v2.1 AF=0.00478% (12/250,878 alleles, 0 homozygotes) and gnomAD v4.1 AF=0.00347% (56/1,614,008 alleles, 0 homozygotes). Both are well below the 0.1% threshold for PM2. The variant is absent from gnomAD-Canada.
Benign criteria applied · 0
No benign criterion marked as applied in the recorded assessment.
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: PVS1 moderate, PM2 supporting; combination = 1 moderate + 1 supporting, 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
56 / 1,614,008 alleles
gnomAD v4.1: 56 / 1,614,008 alleles. Recorded AF 3.46962e-05. Recorded homozygote count 0.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 4.7832e-05; MAF= 0.00478%, 12/250878 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 0.000105764; MAF= 0.01058%, 12/113460 alleles, homozygotes = 0); grpmax FAF= 6.027e-05.
gnomAD-Canada
This variant is present in gnomAD-Canada v1.0 (AF= 0.0002171788467803236, 4/18418 alleles, homozygotes = 0).
SpliceAI score
0.000 maximum delta
Recorded SpliceAI maximum delta score: 0.000. Refer to the recorded PP3/BP4 rationale for interpretation.
No listed criterion applied
SpliceAI ↗
ClinVar submissions
7 reported laboratory submissions
3 Pathogenic · 3 Likely pathogenic · 1 Uncertain significance. ClinVar API review status: criteria provided, multiple submitters, no conflicts.
Context only
ClinVar ↗
Functional evidence
Statement recorded
OncoKB identified variant-specific curated literature and context relevant to functional review; biological-effect context: Likely Loss-of-function; curated oncogenicity label: Likely Oncogenic.
No listed criterion applied
OncoKB ↗
COSMIC
Cancer Hotspots
Somatic evidence
2 recorded samples
This variant has previously been reported in somatic cancers (COSMIC; COSV52073298, n = 2 times).
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 · 19 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
PVS1 at moderate strength: c.2T>C is a start-loss variant abolishing the FANCL initiation codon with no alternative in-frame ATG in exon 1. Loss of function is an established disease mechanism for Fanconi anemia.
PM2 at supporting strength: This variant is present at very low frequency in gnomAD (v2.1 AF=0.00478%; v4.1 AF=0.00347%), with no homozygotes observed, consistent with a rare pathogenic variant.
Overall classification: Uncertain Significance (VUS). The combination of PVS1_Moderate and PM2_Supporting does not meet the threshold for Likely Pathogenic per ACMG/AMP 2015 combination rules (requires ≥2 Moderate or ≥1 Moderate + ≥4 Supporting). ClinVar submissions report Pathogenic/Likely Pathogenic but are limited to single-submitter review and cite evidence not independently verifiable in available full-text literature.
No criteria match.
Met · 2
PVS1 ModerateThis start-loss variant (c.2T>C, p.Met1?) abolishes the initiation codon of FANCL. Loss of function is an established disease mechanism for FANCL (Fanconi anemia, autosomal recessive). Per ClinGen SVI PVS1 recommendations (PMC6185798), initiation codon variants qualify for PVS1 at moderate strength when no alternative in-frame start codon is present in the same exon. No downstream ATG was identified in FANCL exon 1. Details ▾Hide ▴
Evidence considered
- Start-loss variant: c.2T>C changes initiation codon ATG to ACG
- FANCL loss of function causes Fanconi anemia (autosomal recessive)
- No alternative in-frame ATG in exon 1
- ClinGen PVS1 decision tree supports PVS1_Moderate for initiation codon variants without alternative start sites
Still missing
- No experimental confirmation that this specific variant abolishes FANCL protein expression
Sources
PM2 SupportingThis variant is present at very low frequency in population databases: gnomAD v2.1 AF=0.00478% (12/250,878 alleles, 0 homozygotes) and gnomAD v4.1 AF=0.00347% (56/1,614,008 alleles, 0 homozygotes). Both are well below the 0.1% threshold for PM2. The variant is absent from gnomAD-Canada. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1: AF=0.00478%
- 12/250
- 878 alleles
- 0 homozygotes
- gnomAD v4.1: AF=0.00347%
- 56/1
- 614
- 008 alleles
- Highest subpopulation: European (non-Finnish) AF=0.0106%
- Absent from gnomAD-Canada
Sources
Not met · 19 · evaluated, threshold not reached
PS2 No de novo observation reported for this variant in any accessible data source. No parental testing data available. Details ▾Hide ▴
Evidence considered
- No de novo reports in ClinVar
- literature
- or case data
Still missing
- Parental testing data may exist but was not available for review
PS3 No variant-specific functional studies were identified. Reviewed full-text papers (PMID:26149689, PMID:30540754) discuss FANCL domain structure and function at the gene level but do not directly test NM_018062.3:c.2T>C. The OncoKB annotation of Likely Loss-of-function is a curated inference, not experimental functional data for this variant. Details ▾Hide ▴
Evidence considered
- PMID:26149689 — FANCL ELF domain functional characterization
- no variant-specific data
- PMID:30540754 — CRISPR knockout of FANCL in zebrafish
- OncoKB — Likely Loss-of-function annotation (inference
- not experimental)
Still missing
- No experimental functional assay directly testing c.2T>C variant effect on FANCL expression or activity
PS4 No case-control data or statistical enrichment analysis is available. ClinVar submissions reference this variant in individuals with Fanconi anemia and various cancers, but prevalence data in affected versus control populations is not available for independent verification. Details ▾Hide ▴
Evidence considered
- ClinVar submissions report variant in individuals with Fanconi anemia and cancer phenotypes
- No case-control statistical analysis available
Still missing
- Case-control data comparing variant frequency in affected vs. general population would strengthen assessment
Sources
PM1 The variant is located at the initiation codon, a critical functional element. However, this evidence is already captured by PVS1 for this start-loss variant; applying PM1 would constitute double-counting. No independent missense mutational hotspot at this codon was identified. Details ▾Hide ▴
Evidence considered
- Initiation codon (Met1) is critical for translation initiation
- No cancerhotspots.org or literature-defined missense hotspot at this residue
PM6 No de novo observation reported. Same evidence basis as PS2. Details ▾Hide ▴
Evidence considered
- No de novo reports in ClinVar
- literature
- or case data
Still missing
- Parental testing data may exist but was not available for review
PP1 No segregation data available for this variant. Details ▾Hide ▴
Still missing
- Family segregation analysis would be required to assess PP1
PP3 In silico predictions are mixed and inconclusive. REVEL score is 0.212 (below the 0.5 damaging threshold), BayesDel score is 0.66 (above the 0.27 damaging threshold), and SpliceAI predicts no splicing impact (max delta = 0.0). No HCI prior score is available. Multiple predictors do not agree on a deleterious effect. Additionally, missense-focused predictors (REVEL) are not well-calibrated for start-loss variants. Details ▾Hide ▴
Evidence considered
- REVEL: 0.212 (not damaging)
- BayesDel: 0.66 (damaging)
- SpliceAI: max delta 0.00 (no splicing impact)
- HCI prior: not available
Still missing
- In silico predictors are optimized for missense variants
- applicability to start-loss is uncertain
Sources
PP4 ClinVar submissions report this variant in individuals with Fanconi anemia and various cancers. However, the specific patient phenotypes are not independently verifiable from the available evidence. Fanconi anemia has at least 22 genetic etiologies, so the phenotype is not highly specific for a single gene. Without primary clinical data, PP4 cannot be applied. Details ▾Hide ▴
Evidence considered
- ClinVar submissions describe variant in Fanconi anemia and cancer phenotypes
- Primary clinical data not available for independent review
Still missing
- Detailed patient phenotypes from primary literature or clinical records would allow PP4 assessment
Sources
PP5 ClinVar classifies this variant as Pathogenic (VariationID: 566870). However, the review status is 'criteria provided, single submitter' — not 3-star expert panel. Per PP5 application rules, supporting-level evidence requires a 3-star ClinVar expert panel review. This threshold is not met. Details ▾Hide ▴
Evidence considered
- ClinVar classification: Pathogenic (3 pathogenic
- 3 likely pathogenic
- 1 VUS submissions)
- Review status: criteria provided
- single submitter (not 3-star expert panel)
- No ClinGen expert panel review available for FANCL
Still missing
- A 3-star ClinVar expert panel review would elevate PP5 to supporting
Sources
BA1 gnomAD allele frequency (0.00478% v2.1, 0.00347% v4.1) is well below the 1% BA1 threshold. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1 AF=0.00478%
- far below 1% threshold
- gnomAD v4.1 AF=0.00347%
Sources
BS1 gnomAD allele frequency (0.00478% v2.1, 0.00347% v4.1) is well below the 0.3% BS1 threshold. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1 AF=0.00478%
- far below 0.3% threshold
- gnomAD v4.1 AF=0.00347%
Sources
BS2 No evidence that this variant has been observed in a healthy adult individual in the homozygous state, or in trans with a pathogenic variant in a healthy individual. gnomAD shows no homozygotes, and no control cohort data with phenotype annotation is available. Details ▾Hide ▴
Evidence considered
- gnomAD: 0 homozygotes across all populations
- No phenotype data available for gnomAD carriers
Still missing
- Phenotype-annotated control cohorts would be required to assess BS2
Sources
BS3 No functional studies demonstrating no damaging effect for this variant. Reviewed full-text papers do not contain experimental data testing c.2T>C specifically. Details ▾Hide ▴
Still missing
- Functional studies demonstrating normal FANCL expression or activity with c.2T>C would be required
BS4 No segregation data available to assess lack of segregation with disease. Details ▾Hide ▴
Still missing
- Family segregation analysis would be required
BP2 No data on observation in trans with a pathogenic variant in FANCL, a recessive disorder. Without phase information, BP2 cannot be assessed. Details ▾Hide ▴
Still missing
- Phased genotype data showing the variant in trans with a pathogenic FANCL variant in an unaffected individual would be required
BP4 In silico predictions are mixed. REVEL score 0.212 suggests no damaging effect, but BayesDel score 0.66 suggests a damaging effect, and SpliceAI shows no splicing impact. Multiple lines of computational evidence do not consistently suggest no impact on gene product. Consensus for benign prediction is not achieved. Details ▾Hide ▴
Evidence considered
- REVEL: 0.212 (suggests benign)
- BayesDel: 0.66 (suggests damaging)
- SpliceAI: 0.00 (no impact)
- Discordant predictors preclude BP4
Sources
BP5 No evidence of an alternate molecular basis for disease in a case carrying this variant. Details ▾Hide ▴
Still missing
- Data on other genetic findings in individuals carrying this variant would be required
BP6 ClinVar classifies this variant as Pathogenic, not benign. Additionally, the review status is 'criteria provided, single submitter' — not 3-star expert panel. BP6 cannot be applied when the reported classification is pathogenic and the review status does not meet the 3-star threshold. Details ▾Hide ▴
Evidence considered
- ClinVar classification: Pathogenic (not benign)
- Review status: single submitter (not 3-star expert panel)
Sources
PS5 No evidence that this variant has been observed in trans with a known pathogenic variant in FANCL. No phase information available from any data source. Details ▾Hide ▴
Still missing
- Phased genotype data would be required to assess PS5
Not applicable · 5· recorded as not applicable Show reasons ▾Hide reasons ▴
PS1 N/ANo known pathogenic variant at the same nucleotide position (c.2) with a different nucleotide change was identified. Details ▾Hide ▴
No further detail was recorded.
PM5 N/APM5 applies to novel missense variants at the same codon as a known pathogenic missense. This variant (c.2T>C) is a start-loss, not a missense, and no same-residue missense comparators were identified by the pm5_candidates pipeline. Details ▾Hide ▴
No further detail was recorded.
PP2 N/APP2 applies to missense variants in genes with a low rate of benign missense variation and where missense is a common disease mechanism. This is a start-loss variant, not a missense. Details ▾Hide ▴
No further detail was recorded.
BP1 N/ABP1 applies to missense variants in genes where primarily truncating variants cause disease. This is a start-loss variant, which is a truncating-type variant, not a missense. Details ▾Hide ▴
No further detail was recorded.
BP7 N/ABP7 applies to synonymous (silent) variants with no predicted splice impact. This is a start-loss variant (c.2T>C, p.Met1?), not a synonymous variant. Details ▾Hide ▴
No further detail was recorded.
Identifiers
- Gene
- FANCL
- Transcript
- NM_018062.3
- Coding (HGVS c.)
- NM_018062.3:c.2T>C
- Protein (HGVS p.)
- NP_060532.2:p.(Met1?)
- GRCh38
- chr2:58241312 A>G
- GRCh37
- chr2:58468447 A>G
- ClinVar
- 566870
- COSMIC
- COSV52073298
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
56 / 1,614,008 alleles
AF 3.47e-05 · 0 homozygotes · FAF 3.5e-05
gnomAD v2.1
12 / 250,878 alleles
AF 4.78e-05 · 0 homozygotes · FAF 6.03e-05
gnomAD-Canada v1.0
Allele count data not recorded
By genetic ancestry
gnomAD v4.1
AF 3.5e-05 · 56 / 1,614,008 alleles · 0 hom · FAF 3.5e-05
| European (non-Finnish)53 / 1,180,022 | 4.5e-05 |
| Remaining individuals2 / 62,484 | 3.2e-05 |
| European (Finnish)1 / 63,958 | 1.6e-05 |
0 alternate alleles recorded in 7 other groups: Admixed American, Amish, East Asian, Middle Eastern, South Asian, Ashkenazi Jewish, African/African American.
gnomAD v2.1
AF 4.8e-05 · 12 / 250,878 alleles · 0 hom · FAF 6e-05
| European (non-Finnish)12 / 113,460 | 0.00011 |
0 alternate alleles recorded in 7 other groups: African/African American, Admixed American, Ashkenazi Jewish, East Asian, European (Finnish), Remaining individuals, South Asian.
gnomAD-Canada
AF not recorded · ? / ? alleles
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 3.46962e-05; MAF= 0.00347%, 56/1614008 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 4.49144e-05; MAF= 0.00449%, 53/1180022 alleles, homozygotes = 0); grpmax FAF= 3.503e-05.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 4.7832e-05; MAF= 0.00478%, 12/250878 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 0.000105764; MAF= 0.01058%, 12/113460 alleles, homozygotes = 0); grpmax FAF= 6.027e-05.
gnomAD-Canada
This variant is present in gnomAD-Canada v1.0 (AF= 0.0002171788467803236, 4/18418 alleles, homozygotes = 0).
SpliceAI and Pangolin
Other predictors
- REVEL
- 0.212
- BayesDel
- 0.660
How the predictions were used
PP3 In silico predictions are mixed and inconclusive. REVEL score is 0.212 (below the 0.5 damaging threshold), BayesDel score is 0.66 (above the 0.27 damaging threshold), and SpliceAI predicts no splicing impact (max delta = 0.0). No HCI prior score is available. Multiple predictors do not agree on a deleterious effect. Additionally, missense-focused predictors (REVEL) are not well-calibrated for start-loss variants. Details ▾Hide ▴
Evidence considered
- REVEL: 0.212 (not damaging)
- BayesDel: 0.66 (damaging)
- SpliceAI: max delta 0.00 (no splicing impact)
- HCI prior: not available
Still missing
- In silico predictors are optimized for missense variants
- applicability to start-loss is uncertain
Sources
BP4 In silico predictions are mixed. REVEL score 0.212 suggests no damaging effect, but BayesDel score 0.66 suggests a damaging effect, and SpliceAI shows no splicing impact. Multiple lines of computational evidence do not consistently suggest no impact on gene product. Consensus for benign prediction is not achieved. Details ▾Hide ▴
Evidence considered
- REVEL: 0.212 (suggests benign)
- BayesDel: 0.66 (suggests damaging)
- SpliceAI: 0.00 (no impact)
- Discordant predictors preclude BP4
Sources
BP7 N/ABP7 applies to synonymous (silent) variants with no predicted splice impact. This is a start-loss variant (c.2T>C, p.Met1?), not a synonymous variant. 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 = 0.212. BayesDel score = 0.66.
8 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
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PMID 20661450 ↗Sex reversal in zebrafish fancl mutants is caused by Tp53-mediated germ cell apoptosis.Reports sex reversal phenotype in zebrafish fancl mutants. Study uses a fancl mutant line generated by insertional mutagenesis, not the human c.2T>C variant. NM_018062.3:c.2T>C was not identified in this paper.Does not name this variant
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PMID 22720145 ↗Diagnosis of fanconi anemia: mutation analysis by next-generation sequencing.Describes a next-generation sequencing approach for mutation analysis in Fanconi anemia genes. Lists mutations found in FA patients but NM_018062.3:c.2T>C is not among them.Does not name this variant
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PMID 25754594 ↗Loss-of-Function FANCL Mutations Associate with Severe Fanconi Anemia Overlapping the VACTERL Association.Reports three VACTERL cases with loss-of-function FANCL mutations in two families. The specific mutations described do not include NM_018062.3:c.2T>C.Does not name this variant
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PMID 30540754 ↗Multiplexed CRISPR/Cas9-mediated knockout of 19 Fanconi anemia pathway genes in zebrafish revealed their roles in growth, sexual development and fertility.CRISPR/Cas9-mediated knockout of 19 Fanconi anemia pathway genes in zebrafish. Generates fancl-null mutants via indel mutations causing premature truncations, not the human c.2T>C variant. Demonstrates FANCL LOF causes growth defects, sex reversal, and infertility in zebrafish, supporting FANCL LOF as a disease mechanism.Does not name this variant
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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.ACMG/AMP standards and guidelines for sequence variant interpretation. Provides the classification framework but does not discuss NM_018062.3:c.2T>C or any FANCL variant.Does not name this variant
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PMID 26149689 ↗The Fanconi Anemia DNA Repair Pathway Is Regulated by an Interaction between Ubiquitin and the E2-like Fold Domain of FANCL.Miles JA et al. · 2015Characterizes the E2-like fold (ELF) domain of FANCL and its role in regulating the FA DNA repair pathway through ubiquitin interaction. Uses site-directed mutagenesis of specific ELF domain residues but does not test or mention the c.2T>C start-loss variant.Does not name this variant
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PMID 29335925 ↗Germline deleterious mutations in genes other than BRCA2 are infrequent in male breast cancer.Fostira F et al. · 2018Evaluates germline mutations in cancer predisposition genes in male breast cancer. Reports a FANCL deletion but NM_018062.3:c.2T>C is not specifically assessed.Does not name this variant
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PMID 29625052 ↗Pathogenic Germline Variants in 10,389 Adult Cancers.Huang KL et al. · 2018Pan-cancer analysis of pathogenic germline variants in 10,389 adult cancers across 33 cancer types. NM_018062.3:c.2T>C was not specifically identified or discussed.Does not name this variant
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
gnomAD v4.1
56 / 1,614,008 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
3 Pathogenic · 3 Likely pathogenic · 1 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/566870/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/2-58468447-A-G?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr2-58241312-A-G?dataset=gnomad_r4
- gnomAD-Canada ↗http://192.168.4.76:8001/variant/2-58241312-A-G
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_018062.3%3Ac.2T%3…
- OncoKB ↗www.oncokb.org/gene/FANCL/M1?
- COSMIC ↗cancer.sanger.ac.uk/cosmic/mutation/overview?id=150999397
- 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= 3.46962e-05; MAF= 0.00347%, 56/1614008 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 4.49144e-05; MAF= 0.00449%, 53/1180022 alleles, homozygotes = 0); grpmax FAF= 3.503e-05.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 4.7832e-05; MAF= 0.00478%, 12/250878 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 0.000105764; MAF= 0.01058%, 12/113460 alleles, homozygotes = 0); grpmax FAF= 6.027e-05.
gnomAD-Canada
This variant is present in gnomAD-Canada v1.0 (AF= 0.0002171788467803236, 4/18418 alleles, homozygotes = 0).
ClinVar
This variant has been reported in ClinVar as Pathogenic (3 clinical laboratories) and as Likely pathogenic (3 clinical laboratories) and as Uncertain significance (1 clinical laboratory). (ClinVarID = 566870)
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.212. BayesDel score = 0.66.
Functional
OncoKB identified variant-specific curated literature and context relevant to functional review; biological-effect context: Likely Loss-of-function; curated oncogenicity label: Likely Oncogenic.
Somatic
This variant does not lie in a statistically significant hotspot. This variant has previously been reported in somatic cancers (COSMIC; COSV52073298, n = 2 times).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.