chr2-214792458-TAAAA-T

Position:

• chr2-214792458-TAAAA-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_000465.4(BARD1):​c.216-17_216-14del variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000243 in 1,273,170 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 0)
  • Exomes 𝑓: 0.000024 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: BARD1 NM_000465.4 splice_polypyrimidine_tract, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.38

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 Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 31 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BARD1	NM_000465.4	c.216-17_216-14del		splice_polypyrimidine_tract_variant, intron_variant		ENST00000260947.9	NP_000456.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BARD1	ENST00000260947.9	c.216-17_216-14del		splice_polypyrimidine_tract_variant, intron_variant		1	NM_000465.4	ENSP00000260947	P2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 127250 Hom.: 0 Cov.: 0 FAILED QC

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000166 AC: 16 AN: 96390 Hom.: 0 AF XY: 0.000190 AC XY: 10 AN XY: 52578

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000329

Gnomad ASJ exome AF: 0.000379

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.000153

Gnomad NFE exome AF: 0.000208

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000243 AC: 31 AN: 1273170 Hom.: 0 AF XY: 0.0000365 AC XY: 23 AN XY: 630478

Gnomad4 AFR exome AF: 0.0000746

Gnomad4 AMR exome AF: 0.000165

Gnomad4 ASJ exome AF: 0.0000900

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000293

Gnomad4 FIN exome AF: 0.0000781

Gnomad4 NFE exome AF: 0.0000179

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 127250 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 61110

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs56130510; hg19: chr2-215657182;