chr2-214728557-C-T

Position:

• chr2-214728557-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_000465.4(BARD1):​c.*119G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00025 (0 hom., cov: 30)
  • Exomes 𝑓: 0.00045 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: BARD1 NM_000465.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.866

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.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 2-214728557-C-T is Benign according to our data. Variant chr2-214728557-C-T is described in ClinVar as [Benign]. Clinvar id is 801877.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAdExome4 at 235 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BARD1	NM_000465.4	c.*119G>A		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.*119G>A		3_prime_UTR_variant	11/11	1	NM_000465.4	ENSP00000260947	P2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 30 AN: 120766 Hom.: 0 Cov.: 30 FAILED QC

Gnomad AFR AF: 0.0000927

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000853

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00298

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000174

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000452 AC: 235 AN: 520124 Hom.: 0 Cov.: 10 AF XY: 0.000482 AC XY: 127 AN XY: 263462

Gnomad4 AFR exome AF: 0.000480

Gnomad4 AMR exome AF: 0.000559

Gnomad4 ASJ exome AF: 0.000233

Gnomad4 EAS exome AF: 0.000369

Gnomad4 SAS exome AF: 0.00143

Gnomad4 FIN exome AF: 0.000482

Gnomad4 NFE exome AF: 0.000367

Gnomad4 OTH exome AF: 0.000657

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000248 AC: 30 AN: 120806 Hom.: 0 Cov.: 30 AF XY: 0.000209 AC XY: 12 AN XY: 57358

Gnomad4 AFR AF: 0.0000925

Gnomad4 AMR AF: 0.0000852

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00298

Gnomad4 NFE AF: 0.000174

Gnomad4 OTH AF: 0.00

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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.4
DANN	Benign	0.40

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: rs1378645134; hg19: chr2-215593281;