2-214728537-C-CT

Position:

• chr2-214728537-C-CT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_000465.4(BARD1):​c.*138_*139insA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.39 (11459 hom., cov: 0)
  • Exomes 𝑓: 0.37 (848 hom.)
• Consequence: BARD1 NM_000465.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.392

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 -10 ACMG points.

• BP6: Variant 2-214728537-C-CT is Benign according to our data. Variant chr2-214728537-C-CT is described in ClinVar as [Benign]. Clinvar id is 1292322.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.626 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BARD1	NM_000465.4	c.*138_*139insA		3_prime_UTR_variant	11/11	ENST00000260947.9	NP_000456.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BARD1	ENST00000260947.9	c.*138_*139insA		3_prime_UTR_variant	11/11	1	NM_000465.4	ENSP00000260947	P2

Frequencies

GnomAD3 genomes AF: 0.387 AC: 55741 AN: 143882 Hom.: 11461 Cov.: 0

Gnomad AFR AF: 0.265

Gnomad AMI AF: 0.414

Gnomad AMR AF: 0.477

Gnomad ASJ AF: 0.450

Gnomad EAS AF: 0.645

Gnomad SAS AF: 0.480

Gnomad FIN AF: 0.337

Gnomad MID AF: 0.432

Gnomad NFE AF: 0.416

Gnomad OTH AF: 0.417

GnomAD4 exome AF: 0.366 AC: 159483 AN: 435922 Hom.: 848 Cov.: 6 AF XY: 0.365 AC XY: 82593 AN XY: 226016

Gnomad4 AFR exome AF: 0.298

Gnomad4 AMR exome AF: 0.377

Gnomad4 ASJ exome AF: 0.368

Gnomad4 EAS exome AF: 0.441

Gnomad4 SAS exome AF: 0.363

Gnomad4 FIN exome AF: 0.356

Gnomad4 NFE exome AF: 0.363

Gnomad4 OTH exome AF: 0.360

GnomAD4 genome AF: 0.387 AC: 55745 AN: 143908 Hom.: 11459 Cov.: 0 AF XY: 0.389 AC XY: 27078 AN XY: 69594

Gnomad4 AFR AF: 0.265

Gnomad4 AMR AF: 0.478

Gnomad4 ASJ AF: 0.450

Gnomad4 EAS AF: 0.645

Gnomad4 SAS AF: 0.480

Gnomad4 FIN AF: 0.337

Gnomad4 NFE AF: 0.416

Gnomad4 OTH AF: 0.415

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 14, 2019

- -

Computational scores

Source: dbNSFP v4.3

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: rs113789798; hg19: chr2-215593261;