Genetic Information

Gene & Transcript Details

Gene
BARD1
Transcript
NM_000465.4 MANE Select
Total Exons
—
Reference Sequence
NC_000002.11
Alternative Transcripts
IDStatusDetails
NM_000465.3 Alternative 5523 nt | 143–2476
NM_000465.2 Alternative 2610 nt | 136–2469
NM_000465.4 MANE Select 5478 nt | 115–2448
NM_000465.1 Alternative 2530 nt | 74–2407

Variant Details

HGVS Notation
NM_000465.4:c.62G>T
Protein Change
R21L
Location
Exon 1 (Exon 1 of )
1
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
Uncertain Significance (VUS)
1 publications
Clinical Statement

"This variant has been reported in ClinVar as Uncertain significance (1 clinical laboratories)."

COSMIC Somatic Evidence

Open
COSMIC ID
COSM3577420
Recurrence
1 occurrences
PM1 Criteria
Not Applied
COSMIC Database Preview
COSMIC Preview
Accessing full COSMIC database details requires institutional login or subscription.

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 BARD1.

Functional Studies & Therapeutic Relevance

Functional Summary

Error in OpenAI Consolidation. OncoKB: BARD1R21LBARD1R21LSomaticNCBI Gene:580|Show additional gene information Variant OverviewBARD1, a tumor suppressor involved in the DNA damage response, is altered by mutation in breast and ovarian cancers.The BARD1 R21L mutation has not specifically been reviewed by the OncoKB team, and therefore its biological significance is unknown. JAX-CKB: BARD1 R21L does not lie within any known functional domains of the Bard1 protein (UniProt.org). R21L has not been characterized and therefore, its effect on Bard1 protein function is unknown (PubMed, Oct 2025).

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 -208 bp
- Donor Loss (DL) 0.0 -366 bp
+ Acceptor Gain (AG) 0.0 -345 bp
+ Donor Gain (DG) 0.01 -92 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:
PM2

PM2 (Unknown (Pre-LLM))

From pre-LLM assessment (LLM Failed)

BP4

BP4 (Unknown (Pre-LLM))

From pre-LLM assessment (LLM Failed)