About PALB2
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
PALB2 c.721A>G, p.(Asn241Asp)
Classification
Benign
Variant description:
No variant summary was recorded for this case.
Five-step scale from benign to pathogenic. This variant is benign. Select a step to read what it means.
Benign.A benign classification under the recorded framework.
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 ClinGen PALB2 VCEP v1.2.0. 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: 0
Benign evidence criteria: 4
Pathogenic criteria applied · 0
No pathogenic criterion marked as applied in the recorded assessment.
Benign criteria applied · 4
BA1Stand alone
BA1 · stand alone
The grpmax filtering allele frequency in gnomAD v4.1 is 0.58% (FAF 0.00582118), which exceeds the PALB2 VCEP BA1 threshold of >0.1%. This allele frequency is inconsistent with a highly penetrant pathogenic variant for PALB2-related cancer predisposition and meets stand-alone benign criteria.
BS1Strong
BS1 · strong
The grpmax filtering allele frequency in gnomAD v4.1 is 0.58% (FAF 0.00582118), which far exceeds the PALB2 VCEP BS1 threshold of >0.01%. The variant is common in the African/African American population (AF 0.63%) with 3 homozygous individuals observed in gnomAD v4.1, providing strong evidence for a benign interpretation.
BP1Supporting
BP1 · supporting
BP1 applies to all PALB2 missense variants per VCEP guidance: true missense pathogenic variants are thought to be exceedingly rare in PALB2, which has a low rate of non-functional missense variants in relevant assays. This variant is a missense change (p.Asn241Asp).
BP6Supporting
BP6 · supporting
Expert panel ClinGen Hereditary Breast, Ovarian and Pancreatic Cancer Variant Curation Expert Panel, ClinGen classified as Benign.
Recorded classification: Benign
Richards et.al., 2015 - Combining rules v1.2.0 criteria-combination framework: matched Rule17 (1 Benign.Stand Alone) with applied criteria: BA1 stand-alone benign, BS1 strong benign, BP1 supporting benign, BP6 supporting benign; maps to Benign.
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
537 / 1,614,164 alleles
gnomAD v4.1: 537 / 1,614,164 alleles. Recorded AF 0.00033268. Recorded homozygote count 3.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 0.000615807; MAF= 0.06158%, 174/282556 alleles, homozygotes = 2) and has highest observed frequency in the African/African American population (AF= 0.00652699; MAF= 0.65270%, 162/24820 alleles, homozygotes = 2); grpmax FAF= 0.00550914.
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
17 reported laboratory submissions
9 Benign · 8 Likely benign.
Functional evidence
Statement recorded
OncoKB identified variant-specific curated literature and context relevant to functional review; biological-effect context: Inconclusive; curated oncogenicity label: Inconclusive.
No listed criterion applied
OncoKB ↗
COSMIC
Cancer Hotspots
Somatic evidence
1 recorded samples
This variant has previously been reported in somatic cancers (COSMIC; COSV104552978, n = 1 times).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.
Context only
For specialists
Technical detail
ACMG/AMP criteria under ClinGen PALB2 VCEP v1.2.0, with the data and sources behind each one.
26 criteria with recorded statuses: 4 met · 5 not met · 1 not assessed · 16 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
Met
Not met
Not assessed
Not applicable
The PALB2 c.721A>G (p.Asn241Asp) missense variant has an allele frequency of 0.63% in the African/African American population in gnomAD v4.1 (472/75,032 alleles) with 3 homozygous individuals observed. The grpmax filtering allele frequency of 0.58% exceeds the PALB2 VCEP BA1 threshold of >0.1%, meeting stand-alone benign criteria.
The grpmax filtering allele frequency of 0.58% in gnomAD v4.1 far exceeds the PALB2 VCEP BS1 threshold of >0.01%, providing strong benign evidence. This allele frequency is inconsistent with a highly penetrant pathogenic variant for PALB2-related cancer predisposition.
BP1 (supporting benign) is met per PALB2 VCEP v1.2.0, which applies to all PALB2 missense variants given that true missense pathogenic variants are thought to be exceedingly rare in this gene based on published and unpublished functional studies.
This variant has been classified as Benign by the ClinGen Hereditary Breast, Ovarian and Pancreatic Cancer Variant Curation Expert Panel (expert panel review) and is reported as Benign by 9 clinical laboratories and Likely benign by 8 clinical laboratories in ClinVar (VariationID: 126765).
SpliceAI predicts no splice impact (max delta score 0.00). REVEL score is 0.013 and BayesDel score is -0.834, consistent with a benign in silico profile, though these predictors are not used for PALB2 missense variants per VCEP guidance.
PVS1, PS1, PS3, PM1, PP2, and PP3 are not applicable to this missense variant per PALB2 VCEP v1.2.0. PS4, PM2, PP1, and BS4 are not met due to absence of required evidence. Full-text verification of cited publications was attempted but the retrieved full-text files contained only Sci-Hub interface content rather than actual paper text; citation verification was limited to abstracts.
Applying the PALB2 VCEP v1.2.0 final classification rules: BA1 (stand-alone benign) is met, which alone satisfies Rule 17 (>=1 Stand Alone Benign) for a Benign classification. Additionally, BS1 (strong benign) and BP1 (supporting benign) are met, further supporting the benign interpretation.
No criteria match.
Met · 4
BA1 Stand aloneThe grpmax filtering allele frequency in gnomAD v4.1 is 0.58% (FAF 0.00582118), which exceeds the PALB2 VCEP BA1 threshold of >0.1%. This allele frequency is inconsistent with a highly penetrant pathogenic variant for PALB2-related cancer predisposition and meets stand-alone benign criteria. Details ▾Hide ▴
Evidence considered
- gnomAD v4.1: grpmax FAF 0.00582118 (0.58%)
- derived from African/African American subpopulation AF 0.629% (472/75
- 032 alleles
- 3 homozygotes). VCEP BA1 threshold: >0.1%.
Sources
BS1 StrongThe grpmax filtering allele frequency in gnomAD v4.1 is 0.58% (FAF 0.00582118), which far exceeds the PALB2 VCEP BS1 threshold of >0.01%. The variant is common in the African/African American population (AF 0.63%) with 3 homozygous individuals observed in gnomAD v4.1, providing strong evidence for a benign interpretation. Details ▾Hide ▴
Evidence considered
- gnomAD v4.1: grpmax FAF 0.58% > 0.01% VCEP BS1 threshold
- African/African American subpopulation AF 0.63% (472/75
- 032 alleles
- 3 homozygotes). gnomAD v2.1 also supports: grpmax FAF 0.55%
- African/African American AF 0.65% (162/24
- 820 alleles
- 2 homozygotes).
Sources
BP1 SupportingBP1 applies to all PALB2 missense variants per VCEP guidance: true missense pathogenic variants are thought to be exceedingly rare in PALB2, which has a low rate of non-functional missense variants in relevant assays. This variant is a missense change (p.Asn241Asp). Details ▾Hide ▴
Evidence considered
- PALB2 VCEP v1.2.0: BP1 'Apply to all missense variants' with supporting strength
- based on published and unpublished functional studies showing low rate of non-functional PALB2 missense variants.
Sources
Not met · 5 · evaluated, threshold not reached
PS4 No case-control study meeting PALB2 VCEP PS4 thresholds (p-value <= 0.05 AND odds ratio >= 3 OR lower 95% CI >= 1.5) has been identified for this variant. The high population frequency (gnomAD v4.1 grpmax FAF 0.58%) makes significant enrichment in affected individuals over controls unlikely. The ClinGen HBOP VCEP expert panel classified this variant as Benign without applying PS4. Details ▾Hide ▴
Evidence considered
- gnomAD v4.1 grpmax FAF 0.58% argues against case enrichment
- ClinVar expert panel classification Benign cites BS1 not PS4
- exploratory search found no dedicated case-control data.
Still missing
- No formal case-control study comparing variant frequency in PALB2-related cancer cases vs. population controls.
Sources
PM2 The allele frequency in gnomAD v4.1 is 0.03327% (537/1,614,164 alleles), which far exceeds the PALB2 VCEP PM2_Supporting threshold of <=0.000333% (<=1/300,000). This variant is too common in population databases to apply PM2. Details ▾Hide ▴
Evidence considered
- gnomAD v4.1: global AF 0.03327% (537 alleles
- 3 homozygotes)
- VCEP threshold for PM2_Supporting is <=0.000333%.
Sources
PP1 No co-segregation data meeting PALB2 VCEP PP1 thresholds (LOD >= 0.3 or Bayes Factor >= 2:1 for AD condition) has been identified. Anecdotal reports suggest lack of co-segregation in some families where the variant was observed in unaffected relatives, but no formal quantitative analysis is available. Details ▾Hide ▴
Evidence considered
- Exploratory search found no systematic segregation analysis
- anecdotal reports describe non-segregation in some families (PMID:25186627 context).
Still missing
- No formal LOD score or Bayes Factor calculation for co-segregation analysis.
BS4 No quantitative co-segregation analysis meeting PALB2 VCEP BS4 thresholds (LOD <= -1.28 for Strong, LOD <= -0.64 for Moderate, LOD <= -0.32 for Supporting) has been identified. Anecdotal reports of non-segregation (variant absent in some affected relatives) exist but lack statistical rigor required for formal BS4 application. Details ▾Hide ▴
Evidence considered
- Exploratory search identified anecdotal non-segregation in some families but no formal LOD score or Bayes Factor calculation.
Still missing
- No formal LOD score or Bayes Factor calculation for non-segregation analysis.
PS5 No reputable source reports this variant as pathogenic. The ClinVar expert panel (ClinGen HBOP VCEP) classifies it as Benign. Multiple clinical laboratories report it as Benign (9 labs) or Likely benign (8 labs). Details ▾Hide ▴
Evidence considered
- ClinVar: Benign (expert panel)
- Benign (9 labs)
- Likely benign (8 labs)
- no pathogenic assertion from any reputable source.
Sources
Not assessed · 1 · no assessment recorded
BS2 BS2 per PALB2 VCEP requires Fanconi Anemia proband data scored via VCEP BS2 tables and explicitly excludes population cohort data such as gnomAD. No Fanconi Anemia proband data was identified for this variant in the evidence reviewed. Although 3 homozygous individuals are observed in gnomAD v4.1, this cannot be used for VCEP BS2 per VCEP instructions. Details ▾Hide ▴
Evidence considered
- PALB2 VCEP v1.2.0: BS2 requires FA proband data
- gnomAD homozygotes (3 in v4.1) not usable per VCEP instructions.
Still missing
- No Fanconi Anemia proband data identified for BS2 scoring per PALB2 VCEP tables.
Not applicable · 16· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/APVS1 is not applicable to missense variants; this criterion is reserved for null variants (nonsense, frameshift, canonical +/-1,2 splice consensus variants) per the PALB2 PVS1 Decision Tree. This variant is a missense substitution (c.721A>G, p.Asn241Asp). Details ▾Hide ▴
Evidence considered
- PVS1 variant assessment confirms variant bucket 'other' — not a null variant
- PALB2 VCEP PVS1 Decision Tree applies only to null variants.
Sources
pvs1_generic_framework ↗pvs1_variant_assessment
PS1 N/APS1 per PALB2 VCEP is not applicable to missense variants; missense changes are not yet confirmed as a mechanism of disease for PALB2. The PS1 Splicing table applies only to splicing variants. Details ▾Hide ▴
Evidence considered
- PALB2 VCEP v1.2.0: PS1 instructions specify 'Missense: Do not use.'
Sources
PS2 VCEPPS2 is not applicable per PALB2 VCEP v1.2.0; informative de novo occurrences have not yet been observed for autosomal dominant PALB2-related disease. Details ▾Hide ▴
PS3 VCEPPS3 is not applicable per PALB2 VCEP v1.2.0. For protein-level functional studies, the VCEP does not currently endorse PS3 application for PALB2 missense variants. Details ▾Hide ▴
PM1 VCEPPM1 is not applicable per PALB2 VCEP v1.2.0; missense pathogenic variation in PALB2 is not yet confirmed as a mechanism of disease. Details ▾Hide ▴
PM5 N/APM5 per PALB2 VCEP is not applicable to missense variants; it applies only to frameshifting/truncating variants with premature termination codons upstream of p.Tyr1183, or to splice variants meeting specific criteria. Missense changes are not yet confirmed as a mechanism of disease for PALB2. Details ▾Hide ▴
Evidence considered
- PALB2 VCEP v1.2.0: PM5 'Do not use for missense changes'
- pm5_candidates confirms truncation-cutoff mode
- not classic missense PM5.
Sources
cspec ↗pm5_candidates
PM6 VCEPPM6 is not applicable per PALB2 VCEP v1.2.0; informative de novo occurrences have not yet been observed for PALB2-related disease. Details ▾Hide ▴
PP2 VCEPPP2 is not applicable per PALB2 VCEP v1.2.0; missense is not yet confirmed or refuted as a mechanism of disease for PALB2. Details ▾Hide ▴
PP3 N/APP3 per PALB2 VCEP is not applicable to missense variants; published predictors have not yet achieved reliable functional outcome prediction for PALB2 missense variants. The VCEP specifies PP3 only for splicing variants with SpliceAI >= 0.2. This variant has a SpliceAI max delta score of 0.00. Details ▾Hide ▴
Evidence considered
- PALB2 VCEP v1.2.0: PP3 'Missense: Do not use'
- SpliceAI max delta 0.00.
Sources
PP4 VCEPPP4 is not applicable per PALB2 VCEP v1.2.0; breast cancer has multiple genetic etiologies and there are no phenotypic features that can readily distinguish hereditary from sporadic causes. Details ▾Hide ▴
PP5 VCEPPP5 is not for use per PALB2 VCEP as recommended by the ClinGen Sequence Variant Interpretation VCEP Review Committee. Details ▾Hide ▴
BS3 VCEPBS3 is not applicable per PALB2 VCEP v1.2.0. Details ▾Hide ▴
BP2 VCEPBP2 is not applicable per PALB2 VCEP v1.2.0. Details ▾Hide ▴
BP4 N/ABP4 per PALB2 VCEP is not applicable to missense variants; published predictors have not yet achieved reliable functional outcome prediction for PALB2 missense variants. The VCEP specifies BP4 only for splicing variants with SpliceAI <= 0.1. Although this variant has a SpliceAI max delta score of 0.00, BP4 is explicitly not for use with missense variants per VCEP. Details ▾Hide ▴
Evidence considered
- PALB2 VCEP v1.2.0: BP4 'Missense: Do not use'
- SpliceAI max delta 0.00
- REVEL 0.013
- BayesDel -0.834.
Sources
BP5 VCEPBP5 is not applicable per PALB2 VCEP v1.2.0; PALB2 has moderate penetrance and cases with multiple pathogenic variants have been observed with no noticeable difference in phenotype, making this criterion unreliable for PALB2. Details ▾Hide ▴
BP7 N/ABP7 per PALB2 VCEP is applicable to synonymous and deep intronic variants only. This variant is a missense substitution (c.721A>G, p.Asn241Asp), not a synonymous or deep intronic variant. Details ▾Hide ▴
Evidence considered
- PALB2 VCEP v1.2.0: BP7 defined for synonymous and deep intronic variants
- this is a missense variant.
Sources
Identifiers
- Gene
- PALB2
- Transcript
- NM_024675.3
- Coding (HGVS c.)
- NM_024675.3:c.721A>G
- Protein (HGVS p.)
- NP_078951.2:p.(Asn241Asp)
- GRCh38
- chr16:23635825 T>C
- GRCh37
- chr16:23647146 T>C
- ClinVar
- 126765
- COSMIC
- COSV104552978
Gene diagram
Every interpreted variant in PALB2, mapped onto the exon structure of NM_024675.3. Select a row to find it on the plot.
PALB2NM_024675.3
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 PALB2
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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
537 / 1,614,164 alleles
AF 0.000333 · 3 homozygotes · FAF 0.00582
gnomAD v2.1
174 / 282,556 alleles
AF 0.000616 · 2 homozygotes · FAF 0.00551
gnomAD-Canada v1.0
0 / 0 alleles
AF 0 · 0 homozygotes · FAF 0
By genetic ancestry
gnomAD v4.1
AF 0.00033 · 537 / 1,614,164 alleles · 3 hom · FAF 0.0058
| African/African American472 / 75,032 | 0.00633 hom |
| Remaining individuals33 / 62,508 | 0.00053 |
| Admixed American18 / 60,014 | 0.0003 |
| European (non-Finnish)14 / 1,180,034 | 1.2e-05 |
0 alternate alleles recorded in 6 other groups: European (Finnish), Amish, East Asian, Middle Eastern, South Asian, Ashkenazi Jewish.
gnomAD v2.1
AF 0.00062 · 174 / 282,556 alleles · 2 hom · FAF 0.0055
| African/African American162 / 24,820 | 0.00652 hom |
| Remaining individuals2 / 7,202 | 0.00028 |
| Admixed American9 / 35,436 | 0.00025 |
| European (non-Finnish)1 / 129,044 | 7.7e-06 |
0 alternate alleles recorded in 4 other groups: Ashkenazi Jewish, East Asian, European (Finnish), South Asian.
gnomAD-Canada
AF 0 · 0 / 0 alleles · 0 hom
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 0.00033268; MAF= 0.03327%, 537/1614164 alleles, homozygotes = 3) and has highest observed frequency in the African/African American population (AF= 0.00629065; MAF= 0.62906%, 472/75032 alleles, homozygotes = 3); grpmax FAF= 0.00582118.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 0.000615807; MAF= 0.06158%, 174/282556 alleles, homozygotes = 2) and has highest observed frequency in the African/African American population (AF= 0.00652699; MAF= 0.65270%, 162/24820 alleles, homozygotes = 2); grpmax FAF= 0.00550914.
SpliceAI and Pangolin
Other predictors
- REVEL
- 0.013
- BayesDel
- -0.834
How the predictions were used
PP3 N/APP3 per PALB2 VCEP is not applicable to missense variants; published predictors have not yet achieved reliable functional outcome prediction for PALB2 missense variants. The VCEP specifies PP3 only for splicing variants with SpliceAI >= 0.2. This variant has a SpliceAI max delta score of 0.00. Details ▾Hide ▴
Evidence considered
- PALB2 VCEP v1.2.0: PP3 'Missense: Do not use'
- SpliceAI max delta 0.00.
Sources
BP4 N/ABP4 per PALB2 VCEP is not applicable to missense variants; published predictors have not yet achieved reliable functional outcome prediction for PALB2 missense variants. The VCEP specifies BP4 only for splicing variants with SpliceAI <= 0.1. Although this variant has a SpliceAI max delta score of 0.00, BP4 is explicitly not for use with missense variants per VCEP. Details ▾Hide ▴
Evidence considered
- PALB2 VCEP v1.2.0: BP4 'Missense: Do not use'
- SpliceAI max delta 0.00
- REVEL 0.013
- BayesDel -0.834.
Sources
BP7 N/ABP7 per PALB2 VCEP is applicable to synonymous and deep intronic variants only. This variant is a missense substitution (c.721A>G, p.Asn241Asp), not a synonymous or deep intronic variant. Details ▾Hide ▴
Evidence considered
- PALB2 VCEP v1.2.0: BP7 defined for synonymous and deep intronic variants
- this is a missense variant.
Sources
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.013. BayesDel score = -0.834201.
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 21932393 ↗Novel germline PALB2 truncating mutations in African American breast cancer patients.Zheng Y et al. · 2012No paper-specific finding is recorded.
-
PMID 21113654 ↗Germline mutations in PALB2 in African-American breast cancer cases.Ding YC et al. · 2011No paper-specific finding is recorded.
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PMID 23918944 ↗Tamoxifen and risk of contralateral breast cancer for BRCA1 and BRCA2 mutation carriers.No paper-specific finding is recorded.
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PMID 25356972 ↗BRCA1, BRCA2, PALB2, and CDKN2A mutations in familial pancreatic cancer: a PACGENE study.Zhen DB et al. · 2015No paper-specific finding is recorded.
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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.No paper-specific finding is recorded.
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PMID 26467025 ↗A Standardized DNA Variant Scoring System for Pathogenicity Assessments in Mendelian Disorders.No paper-specific finding is recorded.
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PMID 33964450 ↗A Validated Functional Analysis of Partner and Localizer of BRCA2 Missense Variants for Use in Clinical Variant Interpretation.Brnich SE et al. · 2021No paper-specific finding is recorded.
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PMID 28492532 ↗Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.No paper-specific finding is recorded.
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
gnomAD v4.1
537 / 1,614,164 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
9 Benign · 8 Likely benign
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 ↗
ClinGen CSpec
Captured ClinGen CSpec source record
Open source ↗
All source links
- ClinGen CSpec ↗cspec.genome.network/cspec/ui/svi/doc/1526222356
- ClinVar ↗www.ncbi.nlm.nih.gov/clinvar/variation/126765/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/16-23647146-T-C?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr16-23635825-T-C?dataset=gn…
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_024675.3%3Ac.721A…
- OncoKB ↗www.oncokb.org/gene/PALB2/N241D
- COSMIC ↗cancer.sanger.ac.uk/cosmic/mutation/overview?id=120593423
- 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= 0.00033268; MAF= 0.03327%, 537/1614164 alleles, homozygotes = 3) and has highest observed frequency in the African/African American population (AF= 0.00629065; MAF= 0.62906%, 472/75032 alleles, homozygotes = 3); grpmax FAF= 0.00582118.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 0.000615807; MAF= 0.06158%, 174/282556 alleles, homozygotes = 2) and has highest observed frequency in the African/African American population (AF= 0.00652699; MAF= 0.65270%, 162/24820 alleles, homozygotes = 2); grpmax FAF= 0.00550914.
ClinVar
This variant has been reported in ClinVar as Benign (9 clinical laboratories) and as Likely benign (8 clinical laboratories) and as Benign by ClinGen Hereditary Breast, Ovarian and Pancreatic Cancer Variant Curation Expert Panel, ClinGen (expert panel). (ClinVarID = 126765)
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.013. BayesDel score = -0.834201.
Functional
OncoKB identified variant-specific curated literature and context relevant to functional review; biological-effect context: Inconclusive; curated oncogenicity label: Inconclusive.
Somatic
This variant does not lie in a statistically significant hotspot. This variant has previously been reported in somatic cancers (COSMIC; COSV104552978, n = 1 times).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.