2-214809213-C-T

Position:

• chr2-214809213-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000465.4(BARD1):​c.158+199G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.738 in 152,126 control chromosomes in the GnomAD database, including 41,444 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.74 (41444 hom., cov: 33)
• Consequence: BARD1 NM_000465.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.480

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 2-214809213-C-T is Benign according to our data. Variant chr2-214809213-C-T is described in ClinVar as [Benign]. Clinvar id is 1286148.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.785 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BARD1	NM_000465.4	c.158+199G>A		intron_variant		ENST00000260947.9	NP_000456.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BARD1	ENST00000260947.9	c.158+199G>A		intron_variant		1	NM_000465.4	ENSP00000260947	P2

Frequencies

GnomAD3 genomes AF: 0.737 AC: 112073 AN: 152006 Hom.: 41380 Cov.: 33

Gnomad AFR AF: 0.760

Gnomad AMI AF: 0.686

Gnomad AMR AF: 0.784

Gnomad ASJ AF: 0.722

Gnomad EAS AF: 0.805

Gnomad SAS AF: 0.668

Gnomad FIN AF: 0.763

Gnomad MID AF: 0.715

Gnomad NFE AF: 0.711

Gnomad OTH AF: 0.721

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.738 AC: 112195 AN: 152126 Hom.: 41444 Cov.: 33 AF XY: 0.740 AC XY: 55015 AN XY: 74352

Gnomad4 AFR AF: 0.760

Gnomad4 AMR AF: 0.784

Gnomad4 ASJ AF: 0.722

Gnomad4 EAS AF: 0.805

Gnomad4 SAS AF: 0.669

Gnomad4 FIN AF: 0.763

Gnomad4 NFE AF: 0.711

Gnomad4 OTH AF: 0.724

Alfa AF: 0.735 Hom.: 5130

Bravo AF: 0.741

Asia WGS AF: 0.742 AC: 2578 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 22, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.3
DANN	Benign	0.71

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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

Other links and lift over

dbSNP: rs13021937; hg19: chr2-215673937;