Variant 2-214792458-TAAAA-TAAAAA details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_000465.4(BARD1):c.216-14_216-13insT variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0039 ( 2 hom., cov: 0)

Exomes 𝑓: 0.020 ( 0 hom. )

Consequence

BARD1
NM_000465.4 splice_polypyrimidine_tract, intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.884

Variant links:

Genes affected

BARD1 (HGNC:952): (BRCA1 associated RING domain 1) This gene encodes a protein which interacts with the N-terminal region of BRCA1. In addition to its ability to bind BRCA1 in vivo and in vitro, it shares homology with the 2 most conserved regions of BRCA1: the N-terminal RING motif and the C-terminal BRCT domain. The RING motif is a cysteine-rich sequence found in a variety of proteins that regulate cell growth, including the products of tumor suppressor genes and dominant protooncogenes. This protein also contains 3 tandem ankyrin repeats. The BARD1/BRCA1 interaction is disrupted by tumorigenic amino acid substitutions in BRCA1, implying that the formation of a stable complex between these proteins may be an essential aspect of BRCA1 tumor suppression. This protein may be the target of oncogenic mutations in breast or ovarian cancer. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2013]

BARD1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 2-214792458-T-TA is Benign according to our data. Variant chr2-214792458-T-TA is described in ClinVar as [Likely_benign]. Clinvar id is 1198408.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00394 (502/127258) while in subpopulation EAS AF= 0.0095 (40/4212). AF 95% confidence interval is 0.00717. There are 2 homozygotes in gnomad4. There are 239 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.

BS2

High AC in GnomAd4 at 502 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BARD1	NM_000465.4 linkuse as main transcript	c.216-14_216-13insT		splice_polypyrimidine_tract_variant, intron_variant		ENST00000260947.9	NP_000456.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BARD1	ENST00000260947.9 linkuse as main transcript	c.216-14_216-13insT		splice_polypyrimidine_tract_variant, intron_variant		1	NM_000465.4	ENSP00000260947	P2	Q99728-1

Frequencies

GnomAD3 genomes

AF:

0.00394

AC:

501

AN:

127228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00750

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00177

Gnomad ASJ

AF:

0.000650

Gnomad EAS

AF:

0.00947

Gnomad SAS

AF:

0.00267

Gnomad FIN

AF:

0.00778

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00190

Gnomad OTH

AF:

0.00230

GnomAD3 exomes

AF:

0.0148

AC:

1425

AN:

96390

Hom.:

AF XY:

0.0143

AC XY:

751

AN XY:

52578

show subpopulations

Gnomad AFR exome

AF:

0.0192

Gnomad AMR exome

AF:

0.0168

Gnomad ASJ exome

AF:

0.0117

Gnomad EAS exome

AF:

0.0348

Gnomad SAS exome

AF:

0.00874

Gnomad FIN exome

AF:

0.0158

Gnomad NFE exome

AF:

0.0129

Gnomad OTH exome

AF:

0.0102

GnomAD4 exome

AF:

0.0204

AC:

25501

AN:

1250056

Hom.:

Cov.:

AF XY:

0.0197

AC XY:

12220

AN XY:

619326

show subpopulations

Gnomad4 AFR exome

AF:

0.0270

Gnomad4 AMR exome

AF:

0.0156

Gnomad4 ASJ exome

AF:

0.0165

Gnomad4 EAS exome

AF:

0.0288

Gnomad4 SAS exome

AF:

0.0165

Gnomad4 FIN exome

AF:

0.0237

Gnomad4 NFE exome

AF:

0.0203

Gnomad4 OTH exome

AF:

0.0207

GnomAD4 genome

AF:

0.00394

AC:

502

AN:

127258

Hom.:

Cov.:

AF XY:

0.00391

AC XY:

239

AN XY:

61152

show subpopulations

Gnomad4 AFR

AF:

0.00752

Gnomad4 AMR

AF:

0.00176

Gnomad4 ASJ

AF:

0.000650

Gnomad4 EAS

AF:

0.00950

Gnomad4 SAS

AF:

0.00268

Gnomad4 FIN

AF:

0.00778

Gnomad4 NFE

AF:

0.00190

Gnomad4 OTH

AF:

0.00228

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital

Aug 15, 2023

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 19, 2019

- -

Hereditary cancer-predisposing syndrome

Benign:1

Benign, criteria provided, single submitter

curation

Sema4, Sema4

May 27, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over