2-214754055-A-G

Position:

• chr2-214754055-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.1569-1500T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.314 in 152,032 control chromosomes in the GnomAD database, including 7,678 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 0.31 (7678 hom., cov: 32)
• Consequence: BARD1 NM_000465.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.120

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=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.384 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BARD1	NM_000465.4	c.1569-1500T>C		intron_variant		ENST00000260947.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BARD1	ENST00000260947.9	c.1569-1500T>C		intron_variant		1	NM_000465.4	P2

Frequencies

GnomAD3 genomes AF: 0.314 AC: 47661 AN: 151914 Hom.: 7664 Cov.: 32

Gnomad AFR AF: 0.311

Gnomad AMI AF: 0.240

Gnomad AMR AF: 0.283

Gnomad ASJ AF: 0.306

Gnomad EAS AF: 0.349

Gnomad SAS AF: 0.398

Gnomad FIN AF: 0.406

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.301

Gnomad OTH AF: 0.306

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

GnomAD4 genome AF: 0.314 AC: 47700 AN: 152032 Hom.: 7678 Cov.: 32 AF XY: 0.320 AC XY: 23787 AN XY: 74308

Gnomad4 AFR AF: 0.311

Gnomad4 AMR AF: 0.283

Gnomad4 ASJ AF: 0.306

Gnomad4 EAS AF: 0.349

Gnomad4 SAS AF: 0.399

Gnomad4 FIN AF: 0.406

Gnomad4 NFE AF: 0.301

Gnomad4 OTH AF: 0.308

Alfa AF: 0.271 Hom.: 1804

Bravo AF: 0.298

Asia WGS AF: 0.357 AC: 1241 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.1
DANN	Benign	0.55

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: rs1374230; hg19: chr2-215618779;