2-214809599-C-G

Position:

chr2-214809599-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000465.4(BARD1):c.-30G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.715 in 1,529,042 control chromosomes in the GnomAD database, including 391,704 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.74 ( 41389 hom., cov: 35)

Exomes 𝑓: 0.71 ( 350315 hom. )

Consequence

BARD1
NM_000465.4 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.234

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 2-214809599-C-G is Benign according to our data. Variant chr2-214809599-C-G is described in ClinVar as [Benign]. Clinvar id is 334199.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.78 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BARD1	NM_000465.4 link	c.-30G>C		5_prime_UTR_variant	1/11	ENST00000260947.9	NP_000456.2	Q99728-1A0AVN2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BARD1	ENST00000260947.9 link	c.-30G>C		5_prime_UTR_variant	1/11	1	NM_000465.4	ENSP00000260947.4		Q99728-1

Frequencies

GnomAD3 genomes

AF:

0.737

AC:

111994

AN:

152010

Hom.:

41325

Cov.:

show subpopulations

Gnomad AFR

AF:

0.759

Gnomad AMI

AF:

0.685

Gnomad AMR

AF:

0.783

Gnomad ASJ

AF:

0.722

Gnomad EAS

AF:

0.800

Gnomad SAS

AF:

0.667

Gnomad FIN

AF:

0.762

Gnomad MID

AF:

0.715

Gnomad NFE

AF:

0.711

Gnomad OTH

AF:

0.721

GnomAD3 exomes

AF:

0.734

AC:

102538

AN:

139724

Hom.:

37929

AF XY:

0.726

AC XY:

55436

AN XY:

76410

show subpopulations

Gnomad AFR exome

AF:

0.764

Gnomad AMR exome

AF:

0.815

Gnomad ASJ exome

AF:

0.715

Gnomad EAS exome

AF:

0.804

Gnomad SAS exome

AF:

0.664

Gnomad FIN exome

AF:

0.782

Gnomad NFE exome

AF:

0.708

Gnomad OTH exome

AF:

0.713

GnomAD4 exome

AF:

0.712

AC:

980672

AN:

1376914

Hom.:

350315

Cov.:

AF XY:

0.710

AC XY:

481575

AN XY:

677870

show subpopulations

Gnomad4 AFR exome

AF:

0.761

Gnomad4 AMR exome

AF:

0.810

Gnomad4 ASJ exome

AF:

0.711

Gnomad4 EAS exome

AF:

0.767

Gnomad4 SAS exome

AF:

0.668

Gnomad4 FIN exome

AF:

0.782

Gnomad4 NFE exome

AF:

0.707

Gnomad4 OTH exome

AF:

0.718

GnomAD4 genome

AF:

0.737

AC:

112116

AN:

152128

Hom.:

41389

Cov.:

AF XY:

0.739

AC XY:

54998

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.759

Gnomad4 AMR

AF:

0.784

Gnomad4 ASJ

AF:

0.722

Gnomad4 EAS

AF:

0.801

Gnomad4 SAS

AF:

0.668

Gnomad4 FIN

AF:

0.762

Gnomad4 NFE

AF:

0.711

Gnomad4 OTH

AF:

0.724

Alfa

AF:

0.722

Hom.:

7277

Bravo

AF:

0.741

Asia WGS

AF:

0.740

AC:

2572

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

Familial cancer of breast

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Hereditary breast ovarian cancer syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

National Health Laboratory Service, Universitas Academic Hospital and University of the Free State

Apr 19, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

6.0

DANN

Benign

0.40

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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