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.9234C>T (p.Val3078=)

CA026042

142391 (ClinVar)

Gene: BRCA2
Condition: BRCA2-related cancer predisposition
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 0af8d63d-a4ae-4d4a-856c-4c895a1a95f3
Approved on: 2024-06-12
Published on: 2024-06-12

HGVS expressions

NM_000059.4:c.9234C>T
NM_000059.4(BRCA2):c.9234C>T (p.Val3078=)
NC_000013.11:g.32380123C>T
CM000675.2:g.32380123C>T
NC_000013.10:g.32954260C>T
CM000675.1:g.32954260C>T
NC_000013.9:g.31852260C>T
NG_012772.3:g.69644C>T
ENST00000470094.2:c.9234C>T
ENST00000528762.2:c.*601C>T
ENST00000530893.7:c.8865C>T
ENST00000665585.2:c.*796C>T
ENST00000666593.2:c.9234C>T
ENST00000700202.2:c.9183C>T
ENST00000700202.1:c.1650C>T
ENST00000700203.1:n.1361C>T
ENST00000380152.8:c.9234C>T
ENST00000544455.6:c.9234C>T
ENST00000614259.2:c.9242C>T
ENST00000665585.1:c.2112C>T
ENST00000666593.1:c.117C>T
ENST00000680887.1:c.9234C>T
ENST00000380152.7:c.9234C>T
ENST00000470094.1:c.191C>T
ENST00000544455.5:c.9234C>T
NM_000059.3:c.9234C>T
More

Benign

Met criteria codes 3
BP4 BP7_Strong BP5
Not Met criteria codes 3
BA1 BS1 PM2

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.9234C>T variant in BRCA2 is a synonymous variant (p.Val3078=). This variant is present in gnomAD v2.1 (exomes only, non-cancer subset) or gnomAD v3.1 (non-cancer subset) but is below the ENIGMA BRCA1/2 VCEP threshold >0.00002 for BS1_Supporting (PM2_Supporting, BS1, and BA1 are not met). This BRCA2 synonymous (silent) variant is within a key functional domain, and SpliceAI predictor score of 0.00 suggests that the variant has no impact on splicing (score threshold <0.10) (BP4 met). This is a synonymous (silent) variant, and mRNA experimental analysis indicates small or no impact on splicing (PMIDs: 31143303, 20215541 and pers comm E Velasco, Ambry internal contributor), considered strong evidence against pathogenicity (BP7_Strong (RNA)). Multifactorial likelihood ratio analysis using clinically calibrated data produced a combined LR for this variant of 0.055 (based on Family History LR=0.055), within the thresholds for Moderate benign evidence (LR ≥0.05 & <0.23) (BP5_Moderate met; PMID: 31853058). 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 (BP4, BP7_Strong (RNA), BP5_Moderate).
Met criteria codes
BP4
This BRCA2 synonymous (silent) variant is within a key functional domain, and SpliceAI predictor score of 0.00 suggests that the variant has no impact on splicing (score threshold <0.10) (BP4 met).
BP7_Strong
This is a synonymous (silent) variant, and mRNA experimental analysis indicates no impact on splicing (PMID: 31143303, Ambry internal contributor), considered strong evidence against pathogenicity (BP7_Strong (RNA)).
BP5
Multifactorial likelihood ratio analysis using clinically calibrated data produced a combined LR for this variant of 0.055 (based on Family History LR=0.055), within the thresholds for Moderate benign evidence (LR ≥0.05 & <0.23) (BP5_Moderate met; PMID: 31853058).
Not Met criteria codes
BA1
This variant is present in gnomAD v2.1 (exomes only, non-cancer subset) or gnomAD v3.1 (non-cancer subset) but is below the ENIGMA BRCA1/2 VCEP threshold >0.00002 for BS1_Supporting (PM2_Supporting, BS1, and BA1 are not met).
BS1
This variant is present in gnomAD v2.1 (exomes only, non-cancer subset) or gnomAD v3.1 (non-cancer subset) but is below the ENIGMA BRCA1/2 VCEP threshold >0.00002 for BS1_Supporting (PM2_Supporting, BS1, and BA1 are not met).
PM2
This variant is present in gnomAD v2.1 (exomes only, non-cancer subset) or gnomAD v3.1 (non-cancer subset) but is below the ENIGMA BRCA1/2 VCEP threshold >0.00002 for BS1_Supporting (PM2_Supporting, BS1, and BA1 are not met).
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.