chr2-214780322-C-T

Position:

• chr2-214780322-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.1314+238G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.714 in 152,062 control chromosomes in the GnomAD database, including 39,357 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.71 (39357 hom., cov: 32)
• Consequence: BARD1 NM_000465.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0480

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=-0.95).
• BP6: Variant 2-214780322-C-T is Benign according to our data. Variant chr2-214780322-C-T is described in ClinVar as [Benign]. Clinvar id is 1280386.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.772 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BARD1	NM_000465.4	c.1314+238G>A		intron_variant		ENST00000260947.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BARD1	ENST00000260947.9	c.1314+238G>A		intron_variant		1	NM_000465.4	P2

Frequencies

GnomAD3 genomes AF: 0.715 AC: 108577 AN: 151944 Hom.: 39336 Cov.: 32

Gnomad AFR AF: 0.589

Gnomad AMI AF: 0.758

Gnomad AMR AF: 0.718

Gnomad ASJ AF: 0.752

Gnomad EAS AF: 0.793

Gnomad SAS AF: 0.687

Gnomad FIN AF: 0.857

Gnomad MID AF: 0.755

Gnomad NFE AF: 0.761

Gnomad OTH AF: 0.717

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

GnomAD4 genome AF: 0.714 AC: 108645 AN: 152062 Hom.: 39357 Cov.: 32 AF XY: 0.720 AC XY: 53509 AN XY: 74322

Gnomad4 AFR AF: 0.589

Gnomad4 AMR AF: 0.718

Gnomad4 ASJ AF: 0.752

Gnomad4 EAS AF: 0.792

Gnomad4 SAS AF: 0.688

Gnomad4 FIN AF: 0.857

Gnomad4 NFE AF: 0.761

Gnomad4 OTH AF: 0.720

Alfa AF: 0.751 Hom.: 71881

Bravo AF: 0.697

Asia WGS AF: 0.733 AC: 2546 AN: 3476

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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.4
DANN	Benign	0.71

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

Other links and lift over

dbSNP: rs3768708; hg19: chr2-215645046;