Evidence Repository
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.7008-5T>C

CA024740

38078 (ClinVar)

Gene: BRCA2
Condition: BRCA2-related cancer predisposition
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: bebd861e-c31f-4170-ac59-26f4c43cb0f7
Approved on: 2024-06-12
Published on: 2024-06-12

HGVS expressions

NM_000059.4:c.7008-5T>C
NM_000059.4(BRCA2):c.7008-5T>C
NC_000013.11:g.32354856T>C
CM000675.2:g.32354856T>C
NC_000013.10:g.32928993T>C
CM000675.1:g.32928993T>C
NC_000013.9:g.31826993T>C
NG_012772.3:g.44377T>C
ENST00000470094.2:c.7008-5T>C
ENST00000528762.2:c.7008-5T>C
ENST00000530893.7:c.6639-5T>C
ENST00000665585.2:c.7008-5T>C
ENST00000666593.2:c.7008-5T>C
ENST00000700202.2:c.7008-5T>C
ENST00000380152.8:c.7008-5T>C
ENST00000544455.6:c.7008-5T>C
ENST00000614259.2:c.7008-5T>C
ENST00000680887.1:c.7008-5T>C
ENST00000380152.7:c.7008-5T>C
ENST00000544455.5:c.7008-5T>C
ENST00000614259.1:n.7008-5T>C
NM_000059.3:c.7008-5T>C
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Likely Benign

Met criteria codes 2
BP7_Strong PM2_Supporting
Not Met criteria codes 2
BP4 PP3

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.7008-5T>C variant is an intronic variant occurring in intron 13 of the BRCA2 gene. This variant is absent from gnomAD v2.1 (exomes only, non-cancer subset, read depth ≥25) and gnomAD v3.1 (non-cancer subset, read depth ≥25) (PM2_Supporting met). This BRCA2 intronic variant is outside of the native donor and acceptor 1,2 splice sites, and the SpliceAI predictor score of 0.12 indicates that impact on splicing is unclear (score range 0.10-0.20) (PP3 and BP4 not met). This is an intronic variant, and mRNA experimental analysis indicates no impact on splicing (PMID: 31191615), considered strong evidence against pathogenicity (BP7_Strong (RNA)). In summary, this variant meets the criteria to be classified as a Likely benign variant for BRCA2-related cancer predisposition based on the ACMG/AMP criteria applied as specified by the ENIGMA BRCA1/2 VCEP (PM2_Supporting, BP7_Strong (RNA)).
Met criteria codes
BP7_Strong
This is an intronic variant, and mRNA experimental analysis indicates no impact on splicing (PMID: 31191615), considered strong evidence against pathogenicity (BP7_Strong (RNA)).
PM2_Supporting
This variant is absent from gnomAD v2.1 (exomes only, non-cancer subset, read depth ≥25) and gnomAD v3.1 (non-cancer subset, read depth ≥25) (PM2_Supporting met).
Not Met criteria codes
BP4
This BRCA2 intronic variant is outside of the native donor and acceptor 1,2 splice sites, and the SpliceAI predictor score of 0.12 indicates that impact on splicing is unclear (score range 0.10-0.20) (PP3 and BP4 not met).
PP3
This BRCA2 intronic variant is outside of the native donor and acceptor 1,2 splice sites, and the SpliceAI predictor score of 0.12 indicates that impact on splicing is unclear (score range 0.10-0.20) (PP3 and BP4 not met).
Curation History
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