2-214792971-A-G

Position:

• chr2-214792971-A-G

Variant summary

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

The NM_000465.4(BARD1):​c.216-526T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 152,156 control chromosomes in the GnomAD database, including 1,572 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 0.13 (1572 hom., cov: 32)
• Consequence: BARD1 NM_000465.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.989

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.403 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BARD1	NM_000465.4	c.216-526T>C		intron_variant		ENST00000260947.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BARD1	ENST00000260947.9	c.216-526T>C		intron_variant		1	NM_000465.4	P2

Frequencies

GnomAD3 genomes AF: 0.131 AC: 19912 AN: 152038 Hom.: 1569 Cov.: 32

Gnomad AFR AF: 0.145

Gnomad AMI AF: 0.191

Gnomad AMR AF: 0.166

Gnomad ASJ AF: 0.114

Gnomad EAS AF: 0.419

Gnomad SAS AF: 0.160

Gnomad FIN AF: 0.130

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0914

Gnomad OTH AF: 0.121

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

GnomAD4 genome AF: 0.131 AC: 19928 AN: 152156 Hom.: 1572 Cov.: 32 AF XY: 0.137 AC XY: 10179 AN XY: 74412

Gnomad4 AFR AF: 0.145

Gnomad4 AMR AF: 0.166

Gnomad4 ASJ AF: 0.114

Gnomad4 EAS AF: 0.418

Gnomad4 SAS AF: 0.161

Gnomad4 FIN AF: 0.130

Gnomad4 NFE AF: 0.0914

Gnomad4 OTH AF: 0.126

Alfa AF: 0.104 Hom.: 462

Bravo AF: 0.142

Asia WGS AF: 0.274 AC: 953 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	5.9
DANN	Benign	0.46

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: rs3754546; hg19: chr2-215657695;