Genetic Variant BARD1:n.807dupA (chr2-214728537-C-CT) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The ENST00000471590.5(BARD1):n.807dupA variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.39 ( 11459 hom., cov: 0)

Exomes 𝑓: 0.37 ( 848 hom. )

Consequence

BARD1
ENST00000471590.5 non_coding_transcript_exon

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.392

Publications

1 publications found

Variant links:

COSMIC-nc: COSV109417372

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 Gene-Disease associations (from GenCC):

breast cancer
Inheritance: AD Classification: DEFINITIVE Submitted by: G2P
hereditary breast carcinoma
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen
familial ovarian cancer
Inheritance: AD Classification: LIMITED Submitted by: ClinGen
hereditary nonpolyposis colon cancer
Inheritance: AD Classification: LIMITED Submitted by: ClinGen

BARD1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP6

Variant 2-214728537-C-CT is Benign according to our data. Variant chr2-214728537-C-CT is described in ClinVar as [Benign]. Clinvar id is 1292322.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.626 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BARD1	NM_000465.4 link	c.*138dupA		3_prime_UTR_variant	Exon 11 of 11	ENST00000260947.9	NP_000456.2	Q99728-1A0AVN2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BARD1	ENST00000260947.9 link	c.*138dupA		3_prime_UTR_variant	Exon 11 of 11	1	NM_000465.4	ENSP00000260947.4		Q99728-1

Frequencies

GnomAD3 genomes

AF:

0.387

AC:

55741

AN:

143882

Hom.:

11461

Cov.:

show subpopulations

Gnomad AFR

AF:

0.265

Gnomad AMI

AF:

0.414

Gnomad AMR

AF:

0.477

Gnomad ASJ

AF:

0.450

Gnomad EAS

AF:

0.645

Gnomad SAS

AF:

0.480

Gnomad FIN

AF:

0.337

Gnomad MID

AF:

0.432

Gnomad NFE

AF:

0.416

Gnomad OTH

AF:

0.417

GnomAD4 exome

AF:

0.366

AC:

159483

AN:

435922

Hom.:

848

Cov.:

AF XY:

0.365

AC XY:

82593

AN XY:

226016

show subpopulations

African (AFR)

AF:

0.298

AC:

3449

AN:

11560

American (AMR)

AF:

0.377

AC:

5564

AN:

14776

Ashkenazi Jewish (ASJ)

AF:

0.368

AC:

4438

AN:

12076

East Asian (EAS)

AF:

0.441

AC:

11863

AN:

26890

South Asian (SAS)

AF:

0.363

AC:

12093

AN:

33300

European-Finnish (FIN)

AF:

0.356

AC:

8503

AN:

23870

Middle Eastern (MID)

AF:

0.357

AC:

808

AN:

2264

European-Non Finnish (NFE)

AF:

0.363

AC:

104190

AN:

287382

Other (OTH)

AF:

0.360

AC:

8575

AN:

23804

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.433

Heterozygous variant carriers

4942

9885

14827

19770

24712

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.387

AC:

55745

AN:

143908

Hom.:

11459

Cov.:

AF XY:

0.389

AC XY:

27078

AN XY:

69594

show subpopulations

African (AFR)

AF:

0.265

AC:

10446

AN:

39398

American (AMR)

AF:

0.478

AC:

6953

AN:

14556

Ashkenazi Jewish (ASJ)

AF:

0.450

AC:

1537

AN:

3414

East Asian (EAS)

AF:

0.645

AC:

3216

AN:

4986

South Asian (SAS)

AF:

0.480

AC:

2188

AN:

4562

European-Finnish (FIN)

AF:

0.337

AC:

2581

AN:

7666

Middle Eastern (MID)

AF:

0.419

AC:

119

AN:

284

European-Non Finnish (NFE)

AF:

0.416

AC:

27510

AN:

66158

Other (OTH)

AF:

0.415

AC:

821

AN:

1980

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1532

3064

4595

6127

7659

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.305

Hom.:

739

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Aug 14, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.39

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

2-214728537-CTTTTTT-CTTTTTTT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over