Genetic Information

Gene & Transcript Details

Gene
BRCA1
Transcript
NM_007294.4 MANE Select
Total Exons
—
Reference Sequence
NC_000017.10
Alternative Transcripts
IDStatusDetails
NM_007294.4 MANE Select 7088 nt | 114–5705
NM_007294.2 Alternative 7191 nt | 201–5792
NM_007294.3 RefSeq Select 7224 nt | 233–5824

Variant Details

HGVS Notation
NM_007294.4:c.2063del
Protein Change
T688Kfs*13
Location
Exon 10 (Exon 10 of )
10
5'Exon Structure3'
Functional Consequence
Loss of Function
Alternate Identifiers
—

Clinical & Population Data

Population Frequency

gnomAD
Global Frequency
0.0 in 100,000
Extremely Rare
ACMG Criteria Applied PM2
This variant is absent or extremely rare in population databases (PM2 criteria applies).

ClinVar

Open
Classification
Unknown
0 publications
Clinical Statement

""

COSMIC Somatic Evidence

Open
COSMIC ID
Recurrence
0 occurrences
PM1 Criteria
Not Applied
COSMIC Database Preview
COSMIC 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 BRCA1.

Functional Studies & Therapeutic Relevance

Functional Summary

Error in OpenAI Consolidation. OncoKB: BRCA1T688Kfs*13BRCA1T688Kfs*13SomaticNCBI Gene:672|Show additional gene information Variant OverviewBRCA1, a tumor suppressor involved in the DNA damage response, is mutated in various cancer types.The BRCA1 T688Kfs*13 is a truncating mutation in a tumor suppressor gene, and therefore is likely oncogenic.Hide mutation effect description The mutation effect description for truncating mutations in BRCA1 is: Truncating mutations in BRCA1 can lead to varying C-terminally truncated proteins that results in aberrant protein folding, contributing to loss of BRCA1 protein function. Human breast cancer cell lines that contain a truncating mutation in BRCA1 display elevated levels of aneuploidy and impaired DNA damage response. In addition, truncating mutations have been shown to induce aberrant protein localization, which may impact the interaction of important binding partners (PMID: 20608970). Mouse models of BRCA1 truncating mutations develop cancer, including mammary carcinomas, lymphomas and ovarian carcinomas (PMID: 11358863, 12483515, 12947386). 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
Unknown
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 -398 bp
- Donor Loss (DL) 0.0 53 bp
+ Acceptor Gain (AG) 0.0 135 bp
+ Donor Gain (DG) 0.0 389 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:
PVS1

PVS1 (Unknown (Pre-LLM))

From pre-LLM assessment (LLM Failed)

PS3

PS3 (Unknown (Pre-LLM))

From pre-LLM assessment (LLM Failed)

PM2

PM2 (Unknown (Pre-LLM))

From pre-LLM assessment (LLM Failed)