2-214728537-CT-C

Position:

• chr2-214728537-CT-C

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_000465.4(BARD1):​c.*138del 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 0.068 (444 hom., cov: 0)
  • Exomes 𝑓: 0.077 (57 hom.)
• Consequence: BARD1 NM_000465.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• 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 -16 ACMG points.

• BP6: Variant 2-214728537-CT-C is Benign according to our data. Variant chr2-214728537-CT-C is described in ClinVar as [Benign]. Clinvar id is 801875.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.13 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BARD1	NM_000465.4	c.*138del		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.*138del		3_prime_UTR_variant	11/11	1	NM_000465.4	ENSP00000260947	P2

Frequencies

GnomAD3 genomes AF: 0.0679 AC: 9778 AN: 143932 Hom.: 444 Cov.: 0

Gnomad AFR AF: 0.133

Gnomad AMI AF: 0.0487

Gnomad AMR AF: 0.0440

Gnomad ASJ AF: 0.0579

Gnomad EAS AF: 0.000200

Gnomad SAS AF: 0.0137

Gnomad FIN AF: 0.0216

Gnomad MID AF: 0.0617

Gnomad NFE AF: 0.0495

Gnomad OTH AF: 0.0635

GnomAD4 exome AF: 0.0766 AC: 33059 AN: 431740 Hom.: 57 Cov.: 6 AF XY: 0.0761 AC XY: 17034 AN XY: 223748

Gnomad4 AFR exome AF: 0.146

Gnomad4 AMR exome AF: 0.0788

Gnomad4 ASJ exome AF: 0.0824

Gnomad4 EAS exome AF: 0.0333

Gnomad4 SAS exome AF: 0.0601

Gnomad4 FIN exome AF: 0.0453

Gnomad4 NFE exome AF: 0.0810

Gnomad4 OTH exome AF: 0.0847

GnomAD4 genome AF: 0.0680 AC: 9790 AN: 143958 Hom.: 444 Cov.: 0 AF XY: 0.0649 AC XY: 4516 AN XY: 69622

Gnomad4 AFR AF: 0.133

Gnomad4 AMR AF: 0.0439

Gnomad4 ASJ AF: 0.0579

Gnomad4 EAS AF: 0.000201

Gnomad4 SAS AF: 0.0136

Gnomad4 FIN AF: 0.0216

Gnomad4 NFE AF: 0.0495

Gnomad4 OTH AF: 0.0631

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 09, 2019

- -

Familial cancer of breast Benign:1

Benign, criteria provided, single submitter

clinical testing

Mendelics

May 28, 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;