chr2-214725858-C-T

Position:

• chr2-214725858-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000465.4(BARD1):​c.*2818G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.902 in 222,160 control chromosomes in the GnomAD database, including 90,403 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.91 (62678 hom., cov: 30)
  • Exomes 𝑓: 0.89 (27725 hom.)
• Consequence: BARD1 NM_000465.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.132

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.909 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BARD1	NM_000465.4	c.*2818G>A		3_prime_UTR_variant	11/11	ENST00000260947.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BARD1	ENST00000260947.9	c.*2818G>A		3_prime_UTR_variant	11/11	1	NM_000465.4	P2

Frequencies

GnomAD3 genomes AF: 0.908 AC: 137916 AN: 151966 Hom.: 62618 Cov.: 30

Gnomad AFR AF: 0.890

Gnomad AMI AF: 0.925

Gnomad AMR AF: 0.912

Gnomad ASJ AF: 0.890

Gnomad EAS AF: 0.914

Gnomad SAS AF: 0.931

Gnomad FIN AF: 0.968

Gnomad MID AF: 0.835

Gnomad NFE AF: 0.907

Gnomad OTH AF: 0.893

GnomAD4 exome AF: 0.889 AC: 62291 AN: 70076 Hom.: 27725 Cov.: 0 AF XY: 0.888 AC XY: 28731 AN XY: 32360

Gnomad4 AFR exome AF: 0.895

Gnomad4 AMR exome AF: 0.903

Gnomad4 ASJ exome AF: 0.887

Gnomad4 EAS exome AF: 0.838

Gnomad4 SAS exome AF: 0.932

Gnomad4 FIN exome AF: 0.978

Gnomad4 NFE exome AF: 0.900

Gnomad4 OTH exome AF: 0.886

GnomAD4 genome AF: 0.908 AC: 138035 AN: 152084 Hom.: 62678 Cov.: 30 AF XY: 0.912 AC XY: 67800 AN XY: 74360

Gnomad4 AFR AF: 0.890

Gnomad4 AMR AF: 0.912

Gnomad4 ASJ AF: 0.890

Gnomad4 EAS AF: 0.914

Gnomad4 SAS AF: 0.931

Gnomad4 FIN AF: 0.968

Gnomad4 NFE AF: 0.907

Gnomad4 OTH AF: 0.894

Alfa AF: 0.902 Hom.: 85570

Bravo AF: 0.902

Asia WGS AF: 0.921 AC: 3204 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.3
DANN	Benign	0.35

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: rs280621; hg19: chr2-215590582;