0%
BARD1c.562C>TUncertain significance
Print report
Variant interpretation report

BARD1 c.562C>T, p.(Pro188Ser)

NM_000465.4:c.562C>T NP_000456.2:p.(Pro188Ser) View identifiers
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.

About BARD1

No gene-level summary was recorded for this case.

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

This variant is extremely rare in population databases, with an overall allele frequency of 0.00040% (1/249,196 alleles) in gnomAD v2.1 and 0.00012% (2/1,611,936 alleles) in gnomAD v4.1, well below the PM2 threshold of 0.1%. It is absent from gnomAD-Canada. No homozygotes are observed.

Benign criteria applied · 1
BP4Supporting
BP4 · supporting

Multiple lines of computational evidence consistently suggest a benign effect. REVEL score is 0.05 (well below pathogenic threshold), BayesDel score is -0.484 (strongly benign-tending), and SpliceAI predicts no splicing impact (max delta = 0.01). No in silico predictor suggests a 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 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
2 / 1,611,936 alleles

gnomAD v4.1: 2 / 1,611,936 alleles. Recorded AF 1.24074e-06. Recorded homozygote count 0.

gnomAD v2.1

This variant is present in gnomAD v2.1 (AF= 4.01291e-06; MAF= 0.00040%, 1/249196 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 6.15764e-05; MAF= 0.00616%, 1/16240 alleles, homozygotes = 0).

gnomAD-Canada

Absent from gnomAD-Canada v1.0.

Applied · PM2 →
gnomAD v4.1 ↗gnomAD v2.1 ↗gnomAD-Canada ↗
SpliceAI score
0.010 maximum delta

Recorded SpliceAI maximum delta score: 0.010. Refer to the recorded PP3/BP4 rationale for interpretation.

Applied · BP4 → SpliceAI ↗
ClinVar submissions
3 reported laboratory submissions

2 Uncertain significance · 1 Likely benign. ClinVar API review status: criteria provided, conflicting classifications.

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. BARD1, a tumor suppressor involved in the DNA damage response, is altered by mutation in breast and ovarian cancers.

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
COSMIC ↗Cancer Hotspots ↗
For specialists

Technical detail

ACMG/AMP criteria under Not recorded, with the data and sources behind each one.

27 criteria with recorded statuses: 2 met · 21 not met · 0 not assessed · 4 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.

Pathogenic
PVS1PS1PS2PS3PS4PM1PM2PM5PM6PP1PP2PP3PP4PP5PS5
Benign
BA1BS1BS2BS3BS4BP1BP2BP3BP4BP5BP6BP7
Met Not met Not assessed Not applicable

BARD1 c.562C>T (p.Pro188Ser) is a missense variant in exon 4 of the BARD1 gene, a moderate-penetrance hereditary breast cancer susceptibility gene where loss of function is the established disease mechanism.

The variant is extremely rare in population databases, with an allele frequency of 0.00040% in gnomAD v2.1 (1/249,196 alleles) and 0.00012% in gnomAD v4.1 (2/1,611,936 alleles), meeting PM2 at moderate strength.

Multiple computational predictors consistently suggest a benign effect: REVEL score 0.05 (benign-tending), BayesDel score -0.484 (strongly benign-tending), and SpliceAI max delta 0.01 (no predicted splice impact), meeting BP4 at supporting benign strength.

Pro188 is located outside the known critical functional domains of BARD1 (RING finger: aa 46-90; ANK repeats: aa 427-555; BRCT domains: aa 615-777) and is not a statistically significant hotspot residue; PM1 is not met.

The variant is classified as Uncertain significance in ClinVar (2 clinical laboratories) with one additional Likely benign submission (Ambry Genetics), all at 1-star review status. No expert panel classification exists; PP5 and BP6 are not met.

Two breast cancer cohort studies cited in ClinVar (PMID:32866190 and PMID:33646313) were reviewed in full text. BARD1 was mentioned at the gene level in both, but the specific variant c.562C>T (p.Pro188Ser) was not reported in either study. No variant-specific functional, segregation, or case-control data were identified.

Met · 2

PM2 ModerateThis variant is extremely rare in population databases, with an overall allele frequency of 0.00040% (1/249,196 alleles) in gnomAD v2.1 and 0.00012% (2/1,611,936 alleles) in gnomAD v4.1, well below the PM2 threshold of 0.1%. It is absent from gnomAD-Canada. No homozygotes are observed. Details ▾Hide ▴
Evidence considered
  • gnomAD v2.1: AF=4.01e-06 (1/249
  • 196)
  • max subpopulation AF=6.16e-05 (AFR
  • 1/16
  • 240)
  • 0 homozygotes
  • gnomAD v4.1: AF=1.24e-06 (2/1
  • 611
  • 936)
  • max subpopulation AF=1.70e-06 (NFE)
  • grpmax FAF=2.8e-07
  • gnomAD-Canada: absent
Sources
gnomad_v2 ↗gnomad_v4 ↗gnomad_canada ↗
BP4 SupportingMultiple lines of computational evidence consistently suggest a benign effect. REVEL score is 0.05 (well below pathogenic threshold), BayesDel score is -0.484 (strongly benign-tending), and SpliceAI predicts no splicing impact (max delta = 0.01). No in silico predictor suggests a deleterious effect. Details ▾Hide ▴
Evidence considered
  • REVEL: 0.05 — predicts benign (pathogenic threshold typically >0.5)
  • BayesDel: -0.484 — strongly predicts benign (negative score)
  • SpliceAI max delta: 0.01 — predicts no splicing alteration
  • All three independent predictors consistently favor a benign interpretation
Sources
revelbayesdelspliceai ↗

Not met · 21 · evaluated, threshold not reached

PS1 No established pathogenic variant at codon 188 with the same amino acid change (Pro188Ser) was identified. No same-residue pathogenic comparators were found in ClinVar or the literature. Details ▾Hide ▴
Evidence considered
  • PM5 candidate search found zero same-residue comparator variants with pathogenic classification
  • no known pathogenic Pro188Ser or other Pro188 missense change with established pathogenicity was identified.
Sources
pm5_candidates
PS2 No de novo observation was reported for this variant in any reviewed publication. No parental testing data are available. Details ▾Hide ▴
Evidence considered
  • No de novo data found in ClinVar submissions
  • literature pass
  • or full-text review of cited publications.
Still missing
  • No trio or parental testing data available.
PS3 No variant-specific functional studies have been reported. The ClinVar submission (SCV000908589, Color Health) explicitly states 'to our knowledge, functional studies have not been reported for this variant.' No publication identified experimental functional data for Pro188Ser or a systematically characterized range that includes codon 188. Details ▾Hide ▴
Evidence considered
  • ClinVar submission SCV000908589 notes absence of functional studies. Literature review of ClinVar-cited papers (32866190
  • 33646313) found no functional data for this variant.
Still missing
  • No functional assays performed on this variant or a systematically characterized range including codon 188.
Sources
clinvar ↗
PS4 No case-control or cohort enrichment data are available for this variant. The variant was not specifically reported in any of the ClinVar-cited cohort studies (PMID:32866190, PMID:33646313) despite both being breast cancer gene panel screening studies. Prevalence in affected individuals cannot be assessed. Details ▾Hide ▴
Evidence considered
  • Two breast cancer cohort studies cited in ClinVar (32866190
  • 33646313) were reviewed
  • neither specifically reports this variant. The variant is present in gnomAD at extremely low frequency
  • but no affected-vs-control comparison is possible.
Still missing
  • No case-control data
  • no cohort study that explicitly reports this variant's frequency in affected individuals.
PM1 Codon 188 (Pro188) lies outside the known critical functional domains of BARD1 (RING finger: aa 46-90; ANK repeats: aa 427-555; BRCT domains: aa 615-777). Cancer Hotspots analysis confirms this residue is not a statistically significant mutational hotspot. No domain-level PM1 evidence applies. Details ▾Hide ▴
Evidence considered
  • BARD1 domain architecture places Pro188 between the RING domain and ANK repeats. Cancerhotspots.org confirms residue is not a significant hotspot.
PM6 No de novo observation with confirmed maternity and paternity has been reported for this variant. Details ▾Hide ▴
Evidence considered
  • No de novo data found in any reviewed source.
Still missing
  • No trio or parental testing data available.
PP1 No co-segregation data are available for this variant. No family studies were identified in the literature. Details ▾Hide ▴
Evidence considered
  • No co-segregation or family study data found in any reviewed source.
Still missing
  • No family or segregation data available.
PP2 BARD1 is not established as a gene with a low rate of benign missense variation where missense variants are a common disease mechanism. While loss of function is the primary disease mechanism, pathogenic missense variants are documented in BARD1 (primarily in the RING and BRCT domains). Without a gene-specific Z-score or missense constraint metric in the case materials, PP2 cannot be applied. Details ▾Hide ▴
Evidence considered
  • BARD1 missense variants can be pathogenic
  • the gene does not meet the strict PP2 requirement of having a low rate of benign missense variation. No Z-score or missense constraint data provided in case materials.
Still missing
  • No BARD1-specific missense constraint metric (Z-score) available in the case materials.
PP3 Multiple computational predictors consistently suggest a benign effect. REVEL score is 0.05 (well below the typical pathogenic threshold of >0.5), BayesDel score is -0.484 (negative, indicating benign), and SpliceAI max delta is 0.01 (no predicted splice impact). These results do not support a deleterious effect. Details ▾Hide ▴
Evidence considered
  • REVEL score: 0.05 (benign-tending
  • pathogenic threshold typically >0.5)
  • BayesDel score: -0.484 (negative = benign prediction)
  • SpliceAI max delta: 0.01 (no predicted splice alteration)
Sources
revelbayesdelspliceai ↗
PP4 No patient phenotype or family history data specific to this variant are available. The ClinVar-cited publications are cohort-level gene panel screening studies that do not report individual variant-level phenotypes. Details ▾Hide ▴
Evidence considered
  • No variant-specific phenotype or family history data available from any reviewed source.
Still missing
  • No variant-specific clinical phenotype data available.
PP5 ClinVar classification for this variant is Uncertain significance (2 clinical laboratories) and Likely benign (1 clinical laboratory), with review status of 'criteria provided, single submitter' (1-star). No expert panel has classified this variant as pathogenic. No reputable source reports this variant as pathogenic at a level meeting PP5 criteria. Details ▾Hide ▴
Evidence considered
  • ClinVar classification: VUS (2 labs) / Likely benign (1 lab)
  • Review status: 1-star (criteria provided
  • single submitter)
  • No expert panel classification
  • no reputable source reports as pathogenic
  • PP5/BP6 rules: requires ClinVar 3-star EP review or equivalent reputable source reporting as pathogenic
Sources
clinvar ↗
BA1 The maximum observed allele frequency in any population is 0.00616% (African/African American, gnomAD v2.1), which is well below the BA1 threshold of 1%. Details ▾Hide ▴
Evidence considered
  • gnomAD v2.1 max AF: 6.16e-05 (AFR) = 0.00616%
  • gnomAD v4.1 max AF: 1.70e-06 (NFE) = 0.00017%
  • Both far below BA1 threshold of 1%
Sources
gnomad_v2 ↗gnomad_v4 ↗
BS1 The maximum observed allele frequency is 0.00616% (AFR, gnomAD v2.1), well below the non-VCEP BS1 threshold of 0.3%. Details ▾Hide ▴
Evidence considered
  • gnomAD v2.1 max AF: 6.16e-05 = 0.00616% (< 0.3% BS1 threshold)
  • gnomAD v4.1 max AF: 1.70e-06 = 0.00017%
Sources
gnomad_v2 ↗gnomad_v4 ↗
BS2 No observation of this variant in a healthy adult individual has been documented for a fully penetrant disorder. The gnomAD observations are at extremely low frequency and without clinical annotation to establish healthy status. Details ▾Hide ▴
Evidence considered
  • gnomAD observations are at extremely low frequency without clinical phenotype annotation
  • cannot confirm healthy adult carrier status.
Still missing
  • No confirmed healthy adult carrier data available.
BS3 No in vitro or in vivo functional studies demonstrate a benign effect for this variant. The only evidence is computational prediction, which falls under BP4. Details ▾Hide ▴
Evidence considered
  • No experimental functional data identified. Computational predictions addressed under BP4.
Still missing
  • No functional assays performed.
BS4 No segregation data are available for this variant to demonstrate lack of co-segregation with disease. Details ▾Hide ▴
Evidence considered
  • No family or segregation data available to support lack of segregation.
Still missing
  • No segregation data available.
BP1 While BARD1 disease is primarily driven by loss-of-function truncating variants, pathogenic missense variants are well-documented in BARD1 (especially in the RING and BRCT domains). The gene does not meet the BP1 requirement of having truncating variants as the sole or overwhelmingly predominant disease mechanism. Pro188 lies outside the known functional domains, but BP1 requires gene-level evidence that missense variants are not a common disease mechanism. Details ▾Hide ▴
Evidence considered
  • BARD1 has documented pathogenic missense variants
  • gene-level BP1 not met because missense variants are a recognized disease mechanism in this gene.
BP2 No observation of this variant in trans with a known pathogenic variant has been reported. Details ▾Hide ▴
Evidence considered
  • No trans-phase data available.
Still missing
  • No phase data or co-occurrence data available.
BP5 No observation of this variant in a case with an alternate molecular basis for disease has been reported. Details ▾Hide ▴
Evidence considered
  • No data available on alternative molecular diagnoses in carriers.
Still missing
  • No data on co-occurring pathogenic variants in other genes.
BP6 ClinVar reports this variant as Uncertain significance (2 clinical laboratories) and Likely benign (1 clinical laboratory, Ambry Genetics), with a review status of 'criteria provided, single submitter' (1-star). The overall ClinVar classification is VUS. Per PP5/BP6 rules, a 3-star expert panel classification is required for BP6 at supporting benign strength. A 1-star single-submitter Likely benign call does not meet the threshold. Details ▾Hide ▴
Evidence considered
  • ClinVar classification: VUS (2 labs) / Likely benign (1 lab)
  • Review status: 1-star (criteria provided
  • single submitter)
  • No expert panel classification
  • Does not meet 3-star EP threshold for BP6 application
Sources
clinvar ↗
PS5 No in vitro or in vivo functional studies demonstrate a damaging effect for this variant. The only functional evidence signals are computational (REVEL, BayesDel), which fall under PP3/BP4, not PS5. Details ▾Hide ▴
Evidence considered
  • No experimental functional data identified in any reviewed source. Computational predictions are addressed under BP4.
Still missing
  • No functional assays performed.
Not applicable · 4· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/AThis is a missense variant (c.562C>T, p.Pro188Ser), not a null variant (nonsense, frameshift, or canonical splice). The PVS1 variant assessment confirms variant_bucket='other' and does not qualify for the generic PVS1 null-variant framework. Details ▾Hide ▴
Evidence considered
  • PVS1 variant assessment classifies this missense variant as bucket 'other'
  • does not meet null-variant criteria per ClinGen SVI PVS1 recommendations (PMC6185798).
Sources
pvs1_gene_contextpvs1_variant_assessment
PM5 N/ANo pathogenic missense variant at codon 188 with a different amino acid change was identified in ClinVar. The PM5 candidate search returned zero same-residue comparator variants. Details ▾Hide ▴
Evidence considered
  • PM5 candidate harvesting found zero same-residue comparator variants
  • unable to confirm PM5 semantics.
Sources
pm5_candidates
BP3 N/ABP3 applies to in-frame deletions/insertions in repetitive regions; this is a substitution variant. Details ▾Hide ▴

No further detail was recorded.

BP7 N/AThis is a missense variant (c.562C>T, p.Pro188Ser), not a synonymous or intronic variant. BP7 applies only to synonymous variants with no predicted splice impact. Details ▾Hide ▴

No further detail was recorded.

Identifiers

Gene
BARD1
Transcript
NM_000465.4
Coding (HGVS c.)
NM_000465.4:c.562C>T
Protein (HGVS p.)
NP_000456.2:p.(Pro188Ser)
GRCh38
chr2:214781312 G>A
GRCh37
chr2:215646036 G>A
ClinVar
1066134, 232775, 136500

Gene diagram

Every interpreted variant in BARD1, mapped onto the exon structure of NM_000465.4. Select a row to find it on the plot.

BARD1NM_000465.4
Fetching transcript structure from UCSC…
gnomAD v4.1 2 / 1,611,936 alleles AF 1.24e-06 · 0 homozygotes · FAF 2.8e-07
gnomAD v2.1 1 / 249,196 alleles AF 4.01e-06 · 0 homozygotes
gnomAD-Canada v1.0 Allele count data not recorded

By genetic ancestry

gnomAD v4.1

AF 1.2e-06 · 2 / 1,611,936 alleles · 0 hom · FAF 2.8e-07
European (non-Finnish)2 / 1,179,592 1.7e-06
0 alternate alleles recorded in 9 other groups: Remaining individuals, Admixed American, European (Finnish), Amish, East Asian, Middle Eastern, South Asian, Ashkenazi Jewish, African/African American.

gnomAD v2.1

AF 4e-06 · 1 / 249,196 alleles · 0 hom
African/African American1 / 16,240 6.2e-05
0 alternate alleles recorded in 7 other groups: Admixed American, Ashkenazi Jewish, East Asian, European (Finnish), European (non-Finnish), Remaining individuals, South Asian.

Statements

gnomAD v4.1

This variant is present in gnomAD v4.1 (AF= 1.24074e-06; MAF= 0.00012%, 2/1611936 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 1.6955e-06; MAF= 0.00017%, 2/1179592 alleles, homozygotes = 0); grpmax FAF= 2.8e-07.

gnomAD v2.1

This variant is present in gnomAD v2.1 (AF= 4.01291e-06; MAF= 0.00040%, 1/249196 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 6.15764e-05; MAF= 0.00616%, 1/16240 alleles, homozygotes = 0).

gnomAD-Canada

Absent from gnomAD-Canada v1.0.

SpliceAI and Pangolin

SpliceAI acceptor lossat +197 bp
0.010
SpliceAI acceptor gainat +4 bp
0.000
SpliceAI donor lossat +376 bp
0.010
SpliceAI donor gainat +91 bp
0.010
Pangolin splice lossmagnitude shown
-0.000
Pangolin splice gain
0.020

Other predictors

REVEL
0.050
BayesDel
-0.484

How the predictions were used

BP4 SupportingMultiple lines of computational evidence consistently suggest a benign effect. REVEL score is 0.05 (well below pathogenic threshold), BayesDel score is -0.484 (strongly benign-tending), and SpliceAI predicts no splicing impact (max delta = 0.01). No in silico predictor suggests a deleterious effect. Details ▾Hide ▴
Evidence considered
  • REVEL: 0.05 — predicts benign (pathogenic threshold typically >0.5)
  • BayesDel: -0.484 — strongly predicts benign (negative score)
  • SpliceAI max delta: 0.01 — predicts no splicing alteration
  • All three independent predictors consistently favor a benign interpretation
Sources
revelbayesdelspliceai ↗
PP3 Multiple computational predictors consistently suggest a benign effect. REVEL score is 0.05 (well below the typical pathogenic threshold of >0.5), BayesDel score is -0.484 (negative, indicating benign), and SpliceAI max delta is 0.01 (no predicted splice impact). These results do not support a deleterious effect. Details ▾Hide ▴
Evidence considered
  • REVEL score: 0.05 (benign-tending
  • pathogenic threshold typically >0.5)
  • BayesDel score: -0.484 (negative = benign prediction)
  • SpliceAI max delta: 0.01 (no predicted splice alteration)
Sources
revelbayesdelspliceai ↗
BP7 N/AThis is a missense variant (c.562C>T, p.Pro188Ser), not a synonymous or intronic variant. BP7 applies only to synonymous variants with no predicted splice impact. Details ▾Hide ▴

No further detail was recorded.

Statement

In silico

SpliceAI predicts no significant splice impact for this variant (max delta score = 0.01). REVEL score = 0.05. BayesDel score = -0.484308.

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

  • 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.
    Landmark ACMG/AMP guidelines for sequence variant interpretation. This is a methodological standards document; it does not discuss any specific BARD1 variant.
    Does not name this variant
    PMID 25741868 ↗
  • Risk assessment, genetic counseling, and genetic testing for BRCA-related cancer in women: U.S. Preventive Services Task Force recommendation statement.
    Moyer VA et al. · 2014
    U.S. Preventive Services Task Force recommendation on BRCA-related cancer risk assessment and genetic testing. This is a clinical practice guideline document focused on BRCA1/BRCA2; BARD1 is not discussed.
    Does not name this variant
    PMID 24366376 ↗
  • Summaries for patients. Assessing the genetic risk for BRCA-related breast or ovarian cancer in women: recommendations from the U.S. Preventive Services Task Force.
    2014
    Patient summary of the USPSTF BRCA testing recommendation. This is a plain-language summary with no variant-specific content.
    Does not name this variant
    PMID 24366402 ↗
  • PMID 24432435
    Nelson HD et al. · 2013
    No paper-specific finding is recorded.
    PMID 24432435 ↗
  • A practice guideline from the American College of Medical Genetics and Genomics and the National Society of Genetic Counselors: referral indications for cancer predisposition assessment.
    Hampel H et al. · 2015
    ACMG/NSGC practice guideline on referral indications for cancer predisposition assessment. This is a clinical referral guideline that discusses hereditary cancer syndromes at the syndrome level, including BARD1-associated risk, but does not discuss any specific BARD1 variant.
    Does not name this variant
    PMID 25394175 ↗
  • Cancer Genetics Risk Assessment and Counseling (PDQ®): Health Professional Versi
    PDQ cancer genetics risk assessment and counseling summary (Health Professional Version). No abstract or full text available in the case materials; no variant-specific evidence can be derived.
    Does not name this variant
    PMID 26389258 ↗
  • Gene panel screening for insight towards breast cancer susceptibility in different ethnicities.
    Bishop MR et al. · 2020
    Gene panel screening for breast cancer susceptibility in African and European American cohorts (n=97). BARD1 was included in the panel and mentioned at the gene level, but the specific variant NM_000465.4:c.562C>T was not reported in the article text, tables, or supplementary materials.
    Does not name this variant
    PMID 32866190 ↗
  • Gene Sequencing for Pathogenic Variants Among Adults With Breast and Ovarian Cancer in the Caribbean.
    George SHL et al. · 2021
    Multigene panel testing for hereditary breast and ovarian cancer in 1,007 patients from 7 Caribbean countries. BARD1 was included in the gene panel and mentioned at the gene level, but the specific variant NM_000465.4:c.562C>T was not reported in the article text.
    Does not name this variant
    PMID 33646313 ↗

Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.

gnomAD v4.1 2 / 1,611,936 recorded alleles Open source ↗
gnomAD v2.1 Captured gnomAD v2.1 source record Open source ↗
SpliceAI Lookup Recorded maximum delta 0.010 Open source ↗
ClinVar 2 Uncertain significance · 1 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 ↗

All source links

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= 1.24074e-06; MAF= 0.00012%, 2/1611936 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 1.6955e-06; MAF= 0.00017%, 2/1179592 alleles, homozygotes = 0); grpmax FAF= 2.8e-07.

gnomAD v2.1

This variant is present in gnomAD v2.1 (AF= 4.01291e-06; MAF= 0.00040%, 1/249196 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 6.15764e-05; MAF= 0.00616%, 1/16240 alleles, homozygotes = 0).

gnomAD-Canada

Absent from gnomAD-Canada v1.0.

ClinVar

This variant has been reported in ClinVar as Uncertain significance (2 clinical laboratories) and as Likely benign (1 clinical laboratory). (ClinVarID = 232775)

In silico

SpliceAI predicts no significant splice impact for this variant (max delta score = 0.01). REVEL score = 0.05. BayesDel score = -0.484308.

Functional

OncoKB did not identify variant-specific reviewed functional evidence for this variant; gene-level curated context is available for reviewer follow-up. BARD1, a tumor suppressor involved in the DNA damage response, is altered by mutation in breast and ovarian cancers.

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.