Starting

Initialising…

BARD1

Final classification

VUS

BARD1 c.2127A>G · p.Pro709=

BARD1

The BARD1 c.2127A>G (p.Pro709=) variant has not been observed in somatic cancers in COSMIC and has been reported in ClinVar with Likely benign and Benign submissions.

Gene

BARD1

Transcript

NM_000465.4

HGVS · transcript:coding

NM_000465.4:c.2127A>G

Consequence

N/A

GRCh38

chr2:214728883 T>C

GRCh37

chr2:215593607 T>C

Basis Generic ACMG/AMP 2015 final-classification combination rules were used as the applicable fallback framework because no usable official VCEP/CSPEC or local custom gene-specific final-classification framework was present. ▾

Generic ACMG/AMP 2015 final-classification combination rules were used as the applicable fallback framework because no usable official VCEP/CSPEC or local custom gene-specific final-classification framework was present.

Classification rationale

BP7 VUS

BARD1 c.2127A>G

The BARD1 c.2127A>G (p.Pro709=) variant has not been observed in somatic cancers in COSMIC and has been reported in ClinVar with Likely benign and Benign submissions.¹ This variant is absent from gnomAD v2.1 and gnomAD v4.1, with an observed allele frequency of 0, which is below the benign frequency thresholds and does not by itself support pathogenicity for a synonymous variant.² In silico analysis predicts no meaningful splice effect, with a SpliceAI maximum delta score of 0.00, and the variant is synonymous at p.Pro709=, supporting BP7 and not supporting PP3.³

BP7 → VUS

1 cosmicclinvar ↗

2 gnomad_v2 ↗gnomad_v4 ↗

3 spliceai ↗prefetch

Gene diagram · NM_000465.4 · variants mapped to exon structure

BARD1 NM_000465.4

Fetching transcript structure from UCSC…

Applied criteria · 1 met · select any tile

Met

Not met

Not assessed

N/A

Strength very strong supporting

Pathogenic evidence

PVS

Benign evidence

—

Rationale

Select a criterion.

Sources

Evidence used

Gaps remaining

Rule

—

Research & evidence

Population frequency

gnomAD v4.1

gnomAD v2.1

v4.1

Absent from gnomAD v4.1.

v2.1

Absent from gnomAD v2.1.

Allele frequency by ancestry

three datasets · side by side

gnomAD v4.1

Absent · 0 / ?
0 hom

Not observed in any ancestry group.

gnomAD v2.1

Absent · 0 / ?
0 hom

Not observed in any ancestry group.

gnomAD v4 ↗ gnomAD v2 ↗

ClinVar

This variant has been reported in ClinVar as Likely benign (2 clinical laboratories) and as Benign (1 clinical laboratory).

ClinVar ↗

In silico

SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00).

SpliceAI ↗

Functional Unknown Oncogenic Effect

OncoKB oncogenicity for this specific variant: Unknown Oncogenic Effect (variant has not been individually curated).

OncoKB ↗

COSMIC

Cancer hotspots

Somatic evidence Not in COSMIC / hotspots

COSMIC

This variant does not lie in a statistically significant hotspot. This variant has not previously been reported in somatic cancers (COSMIC).

Hotspots

This variant does not lie in a statistically significant hotspot.

Hotspots ↗

Literature · how each cited paper was used

1papers cited

Each card is an audit: what was searched, what was found, whether it names the variant, which criteria it fed, and why.

Customizing local and systemic therapies for women with early breast cancer: the

PMID 34242744 ↗

Found

Structured finding pending for this record — see source link.

Applied to

→BP7 supports · met

Sources & reference links

6Sources

ClinVar

gnomAD v2.1

gnomAD v4.1

SpliceAI

OncoKB

Cancer hotspots