The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • No CSPEC computer assertion could be determined for this classification!


Variant: NM_000059.4(BRCA2):c.7806-40A>G

CA025290

52419 (ClinVar)

Gene: BRCA2
Condition: BRCA2-related cancer predisposition
Inheritance Mode: Autosomal dominant inheritance
UUID: 1b6bf8cf-9d97-4c3a-b53f-3575e8abbf2e
Approved on: 2024-06-12
Published on: 2024-06-12

HGVS expressions

NM_000059.4:c.7806-40A>G
NM_000059.4(BRCA2):c.7806-40A>G
NC_000013.11:g.32362483A>G
CM000675.2:g.32362483A>G
NC_000013.10:g.32936620A>G
CM000675.1:g.32936620A>G
NC_000013.9:g.31834620A>G
NG_012772.3:g.52004A>G
ENST00000470094.2:c.7806-40A>G
ENST00000528762.2:c.7806-40A>G
ENST00000530893.7:c.7437-40A>G
ENST00000665585.2:c.7806-40A>G
ENST00000666593.2:c.7806-40A>G
ENST00000700202.2:c.7806-40A>G
ENST00000700202.1:c.273-40A>G
ENST00000380152.8:c.7806-40A>G
ENST00000544455.6:c.7806-40A>G
ENST00000614259.2:c.7806-32A>G
ENST00000665585.1:c.371-40A>G
ENST00000680887.1:c.7806-40A>G
ENST00000380152.7:c.7806-40A>G
ENST00000544455.5:c.7806-40A>G
ENST00000614259.1:n.7806-32A>G
NM_000059.3:c.7806-40A>G
More

Benign

Met criteria codes 5
BA1 BS2 BP4 BP5_Strong BP7_Strong

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specification: ClinGen ENIGMA BRCA1 and BRCA2 Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for BRCA2 Version 1.0.0

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
ENIGMA BRCA1 and BRCA2 VCEP
The c.7806-40A>G variant is an intronic variant occurring in intron 16 of the BRCA2 gene. The highest non-cancer, non-founder population filter allele frequency in gnomAD v2.1 (exomes only, non-cancer subset, read depth ≥20) or gnomAD v3.1 (non-cancer subset, read depth ≥20) is 0.02867 in the African/African American population, which is above the ENIGMA BRCA1/2 VCEP threshold (>0.001) for BA1 (BA1 met). This BRCA2 intronic variant is outside of the native donor and acceptor 1,2 splice sites, and SpliceAI predictor score of 0.00 suggests that the variant has no impact on splicing (score threshold <0.10) (BP4 met). This is an intronic variant, and mRNA experimental analysis indicates no impact on splicing (PMID: 22505045), considered strong evidence against pathogenicity (BP7_Strong (RNA)). This variant has been observed in >10 individuals with features considered inconsistent with an FA-associated phenotype, and (Likely) Pathogenic variant seen in trans or variant is homozygous (total score >4 points) (BS2 met; Invitae internal contributor). Multifactorial likelihood ratio analysis using clinically calibrated data produced a combined LR for this variant of 0.008 (based on Pathology LR=0.81; Case-Control LR=0.0095), within the thresholds for Strong benign evidence (LR ≥0.00285 & <0.05) (BP5_Strong met; Internal lab contributors). In summary, this variant meets the criteria to be classified as a Benign variant for BRCA2-related cancer predisposition based on the ACMG/AMP criteria applied as specified by the ENIGMA BRCA1/2 VCEP (BA1, BP4, BP7_Strong (RNA), BS2, BP5_Strong).
Met criteria codes
BA1
The highest non-cancer, non-founder population filter allele frequency in gnomAD v2.1 (exomes only, non-cancer subset, read depth ≥20) or gnomAD v3.1 (non-cancer subset, read depth ≥20) is 0.02867 in the African/African American population, which is above the ENIGMA BRCA1/2 VCEP threshold (>0.001) for BA1 (BA1 met).
BS2
This variant has been observed in >10 individuals with features considered inconsistent with an FA-associated phenotype, and (Likely) Pathogenic variant seen in trans or variant is homozygous (total score >4 points) (BS2 met; Invitae internal contributor).
BP4
This BRCA2 intronic variant is outside of the native donor and acceptor 1,2 splice sites, and SpliceAI predictor score of 0.00 suggests that the variant has no impact on splicing (score threshold <0.10) (BP4 met).
BP5_Strong
Multifactorial likelihood ratio analysis using clinically calibrated data produced a combined LR for this variant of 0.008 (based on Pathology LR=0.81; Case-Control LR=0.0095), within the thresholds for Strong benign evidence (LR ≥0.00285 & <0.05) (BP5_Strong met; Internal lab contributors).
BP7_Strong
This is an intronic variant, and mRNA experimental analysis indicates no impact on splicing (PMID: 22505045), considered strong evidence against pathogenicity (BP7_Strong (RNA)).
Curation History
The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.
¤ Powered by BCM's Genboree.