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 label mismatch: BRCA2 vs undefined
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • No CSPEC computed assertion could be determined for this classification!

Variant: NM_000059.4(BRCA2):c.2482T>C (p.Tyr828His)

CA16614121

409559 (ClinVar)

Gene: BRCA2
Condition: BRCA2-related cancer predisposition
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 6426f9fd-2db3-4230-82b0-6e3a10b14da3
Approved on: 2025-05-23
Published on: 2025-05-23

HGVS expressions

NM_000059.4:c.2482T>C
NM_000059.4(BRCA2):c.2482T>C (p.Tyr828His)
NC_000013.11:g.32336837T>C
CM000675.2:g.32336837T>C
NC_000013.10:g.32910974T>C
CM000675.1:g.32910974T>C
NC_000013.9:g.31808974T>C
NG_012772.3:g.26358T>C
ENST00000470094.2:c.2482T>C
ENST00000528762.2:c.2482T>C
ENST00000530893.7:c.2113T>C
ENST00000665585.2:c.2482T>C
ENST00000666593.2:c.2482T>C
ENST00000700202.2:c.2482T>C
ENST00000380152.8:c.2482T>C
ENST00000544455.6:c.2482T>C
ENST00000614259.2:c.2482T>C
ENST00000680887.1:c.2482T>C
ENST00000380152.7:c.2482T>C
ENST00000544455.5:c.2482T>C
ENST00000614259.1:n.2482T>C
NM_000059.3:c.2482T>C
More

Likely Benign

Met criteria codes 1
BP1_Strong
Not Met criteria codes 9
PM2 BS4 BS3 BS1 BP5 PS3 BA1 PP4 PP1

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 1.2.0

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
ENIGMA BRCA1 and BRCA2 VCEP
The c.2482T>C variant in BRCA2 is a missense variant predicted to cause substitution of Tyrosine by Histidine at amino acid 828 (p.(Tyr828His)). 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 missense variant is located outside of a key functional domain and was not predicted to alter mRNA splicing using SpliceAI (score 0.00, score threshold ≤0.1) (BP1_Strong met). 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 (v1.2) (BP1_Strong).
Met criteria codes
BP1_Strong
This missense variant is located outside of a key functional domain and was not predicted to alter mRNA splicing using SpliceAI (score 0.00, score threshold ≤0.1) (BP1_Strong met).
Not Met criteria codes
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).
BS4
No LR/segregations studies for this variant.
BS3
No calibrated studies as of v1.2.0
BS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP5
No LR/segregations studies for this variant.
PS3
No calibrated studies as of v1.2.0
BA1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP4
No LR/segregations studies for this variant.
PP1
No LR/segregations studies for this variant.
Curation History
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