2-214792458-TAAAA-TAAAAAA

Position:

• chr2-214792458-TAAAA-TAAAAAA

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_000465.4(BARD1):​c.216-14_216-13insTT variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000086 (1 hom., cov: 0)
  • Exomes 𝑓: 0.00014 (0 hom.)
• Consequence: BARD1 NM_000465.4 splice_polypyrimidine_tract, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.884

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 -6 ACMG points.

• BP6: Variant 2-214792458-T-TAA is Benign according to our data. Variant chr2-214792458-T-TAA is described in ClinVar as [Likely_benign]. Clinvar id is 2575125.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 11 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BARD1	NM_000465.4	c.216-14_216-13insTT		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.216-14_216-13insTT		splice_polypyrimidine_tract_variant, intron_variant		1	NM_000465.4	ENSP00000260947	P2

Frequencies

GnomAD3 genomes AF: 0.0000864 AC: 11 AN: 127246 Hom.: 1 Cov.: 0

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: 0.000485

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000152

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000249 AC: 24 AN: 96390 Hom.: 0 AF XY: 0.000285 AC XY: 15 AN XY: 52578

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000411

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000150

Gnomad SAS exome AF: 0.000289

Gnomad FIN exome AF: 0.000306

Gnomad NFE exome AF: 0.000277

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000135 AC: 172 AN: 1272380 Hom.: 0 Cov.: 0 AF XY: 0.000157 AC XY: 99 AN XY: 630136

Gnomad4 AFR exome AF: 0.000112

Gnomad4 AMR exome AF: 0.000207

Gnomad4 ASJ exome AF: 0.000135

Gnomad4 EAS exome AF: 0.000150

Gnomad4 SAS exome AF: 0.000264

Gnomad4 FIN exome AF: 0.000182

Gnomad4 NFE exome AF: 0.000119

Gnomad4 OTH exome AF: 0.000210

GnomAD4 genome AF: 0.0000864 AC: 11 AN: 127276 Hom.: 1 Cov.: 0 AF XY: 0.0000818 AC XY: 5 AN XY: 61160

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000487

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000152

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital

Aug 15, 2023

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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;