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.68-7del

CA024535

52188 (ClinVar)

Gene: BRCA2
Condition: BRCA2-related cancer predisposition
Inheritance Mode: Autosomal dominant inheritance
UUID: ae883dc2-3266-494c-88fd-5231ac12a103
Approved on: 2024-06-12
Published on: 2024-06-12

HGVS expressions

NM_000059.4:c.68-7del
NM_000059.4(BRCA2):c.68-7del
NC_000013.11:g.32319070del
CM000675.2:g.32319070del
NC_000013.10:g.32893207del
CM000675.1:g.32893207del
NC_000013.9:g.31791207del
NG_012772.3:g.8591del
NG_017006.2:g.1303del
ENST00000470094.2:c.68-7del
ENST00000528762.2:c.68-7del
ENST00000530893.7:c.-302-7del
ENST00000665585.2:c.68-7del
ENST00000666593.2:c.68-7del
ENST00000700202.2:c.68-7del
ENST00000700200.1:n.191+2543del
ENST00000700201.1:c.68-7del
ENST00000380152.8:c.68-7del
ENST00000544455.6:c.68-7del
ENST00000614259.2:c.68-7del
ENST00000680887.1:c.68-7del
ENST00000380152.7:c.68-7del
ENST00000530893.6:n.266-7del
ENST00000544455.5:c.68-7del
ENST00000614259.1:n.68-7del
NM_000059.3:c.68-7del
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Benign

Met criteria codes 5
BP7_Strong BS1_Supporting BS3 BP4 BP5

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.68-7del variant is an intronic variant occurring in intron 2 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 0.00002293 in the Latino/Admixed American population which is within the ENIGMA BRCA1/2 VCEP threshold (>0.00002 to ≤ 0.0001) for BS1_Supporting (BS1_Supporting met). This BRCA2 intronic variant is outside of the native donor and acceptor 1,2 splice sites, and SpliceAI predictor score of 0.04 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 (PMIDs: 10534775, 21673748, 22505045), considered strong evidence against pathogenicity (BP7_Strong (RNA)). Reported by one calibrated study to exhibit protein function similar to benign control variants (PMID: 35979650) (BS3 met). Multifactorial likelihood ratio analysis using clinically calibrated data produced a combined LR for this variant of 0.32 (based on Pathology LR=0.32), within the thresholds for Supporting benign evidence (LR 0.23-0.48) (BP5 met; PMID: 35979650). 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 (BS1_Supporting, BP4, BP7_Strong (RNA), BS3, BP5).
Met criteria codes
BP7_Strong
This is an intronic variant, and mRNA experimental analysis indicates no impact on splicing (PMIDs: 10534775, 21673748, 22505045), considered strong evidence against pathogenicity (BP7_Strong (RNA)).
BS1_Supporting
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 0.00002293 in the Latino/Admixed American population which is within the ENIGMA BRCA1/2 VCEP threshold (>0.00002 to ≤ 0.0001) for BS1_Supporting (BS1_Supporting met).
BS3
Reported by one calibrated study to exhibit protein function similar to benign control variants (PMID: 35979650) (BS3 met).
BP4
This BRCA2 intronic variant is outside of the native donor and acceptor 1,2 splice sites, and SpliceAI predictor score of 0.04 suggests that the variant has no impact on splicing (score threshold <0.10) (BP4 met).
BP5
Multifactorial likelihood ratio analysis using clinically calibrated data produced a combined LR for this variant of 0.32 (based on Pathology LR=0.32), within the thresholds for Supporting benign evidence (LR 0.23-0.48) (BP5 met; PMID: 35979650).
Curation History
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