Genetic Information

Gene & Transcript Details

Gene
BRCA2
Transcript
NM_000059.3 MANE Select
Total Exons
—
Reference Sequence
NC_000013.10
Alternative Transcripts
IDStatusDetails
NM_000059.4 MANE Select 11954 nt | 200–10456
NM_000059.2 Alternative 11386 nt | 228–10484
NM_000059.3 RefSeq Select 11386 nt | 228–10484

Variant Details

HGVS Notation
NM_000059.3:c.8149G>T
Protein Change
A2717S
Location
Exon 18 (Exon 18 of )
18
5'Exon Structure3'
Functional Consequence
Loss of Function
Alternate Identifiers
—

Clinical & Population Data

Population Frequency

gnomAD
Global Frequency
0.111 in 100,000
Extremely Rare
ACMG Criteria Applied None

ClinVar

Open
Classification
Uncertain Significance (VUS)
4 publications
Publications List
PMID: 15131399

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.

PMID: 22703879

This submission and the accompanying classification are no longer maintained by the submitter. For more information on current observations and classification, please contact variantquestions@myriad.com.

Clinical Statement

"This variant has been reported in ClinVar as Benign (22 clinical laboratories) and as Uncertain significance (2 clinical laboratories) and as Likely benign (11 clinical laboratories) and as Likely Benign (1 clinical laboratories) and as Benign by ClinGen ENIGMA BRCA1 and BRCA2 Variant Curation Expert Panel, ClinGen expert panel."

COSMIC Somatic Evidence

Open
COSMIC ID
COSM6986859
Recurrence
3 occurrences
PM1 Criteria
Not Applied
COSMIC Database Preview
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Functional Impact & Domains

Functional Domain

Hotspot Status
Not a hotspot
Domain Summary
This variant is not located in a mutational hotspot or critical domain.
Related Variants in This Domain
No evidence of other pathogenic variants at this position in gene BRCA2.

Functional Studies & Therapeutic Relevance

Functional Summary

Error in OpenAI Consolidation. OncoKB: BRCA2A2717SBRCA2A2717SSomaticNCBI Gene:675|Show additional gene information Variant OverviewBRCA2, a tumor suppressor involved in the DNA damage response, is mutated in various cancer types.The BRCA2 A2717S mutation is likely neutral.Hide mutation effect description The BRCA2 A2717S mutation is located in the C-terminal domain of the protein. In a study of BRCA2 variants from Australian families with breast cancer, BRCA2 A2717S was predicted to be a neutral variant. This prediction was based on protein modeling, co-occurrence and pedigree causality analysis (PMID: 18375895). Expression of this mutation in a BRCA-deficient cell line demonstrated that it is likely neutral as measured by homologous recombination (HR) DNA-repair activity in an in vitro homology-directed DNA repair (HDR) assay comparable to wildtype BRCA2 (PMID: 29394989). JAX-CKB: No results found

Database Previews
OncoKB
OncoKB Preview
JAX-CKB
JAX-CKB Preview

Click on previews to view full database entries. External databases may require institutional access.

Computational Analysis

Pathogenicity Predictions

SpliceAI
Predictor Consensus
Mixed/VUS
PP3 Applied
No
REVEL Score
0.0
Threshold: ≥0.75 = PP3 applied

SpliceAI Scores

Window: ±500bp
Effect Type Score Position
- Acceptor Loss (AL) 0.0 -172 bp
- Donor Loss (DL) 0.0 182 bp
+ Acceptor Gain (AG) 0.03 19 bp
+ Donor Gain (DG) 0.0 -15 bp
High impact (≥0.5) Medium impact (0.2-0.49) Low impact (<0.2)

VCEP Guidelines

Applied ACMG/AMP Criteria (VCEP Specific)

Filter Criteria:
PS3

PS3 (Unknown (Pre-LLM))

From pre-LLM assessment (LLM Failed)

BP4

BP4 (Unknown (Pre-LLM))

From pre-LLM assessment (LLM Failed)