2-214728552-TGA-T

Position:

• chr2-214728552-TGA-T

Variant summary

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

The NM_000465.4(BARD1):​c.*122_*123del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000401 in 760,112 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00075 (0 hom., cov: 18)
  • Exomes 𝑓: 0.00040 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: BARD1 NM_000465.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.114

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 2-214728552-TGA-T is Benign according to our data. Variant chr2-214728552-TGA-T is described in ClinVar as [Benign]. Clinvar id is 801876.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAdExome4 at 305 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BARD1	NM_000465.4	c.*122_*123del		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.*122_*123del		3_prime_UTR_variant	11/11	1	NM_000465.4	ENSP00000260947	P2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 113 AN: 150372 Hom.: 0 Cov.: 18 FAILED QC

Gnomad AFR AF: 0.000271

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000661

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00436

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000829

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000401 AC: 305 AN: 760112 Hom.: 1 AF XY: 0.000431 AC XY: 167 AN XY: 387156

Gnomad4 AFR exome AF: 0.00124

Gnomad4 AMR exome AF: 0.000768

Gnomad4 ASJ exome AF: 0.000413

Gnomad4 EAS exome AF: 0.000310

Gnomad4 SAS exome AF: 0.00112

Gnomad4 FIN exome AF: 0.000325

Gnomad4 NFE exome AF: 0.000306

Gnomad4 OTH exome AF: 0.000275

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000751 AC: 113 AN: 150486 Hom.: 0 Cov.: 18 AF XY: 0.000626 AC XY: 46 AN XY: 73528

Gnomad4 AFR AF: 0.000270

Gnomad4 AMR AF: 0.0000660

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00436

Gnomad4 NFE AF: 0.000829

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0345 Hom.: 0

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

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: rs1310441861; hg19: chr2-215593276;