2-214728537-C-CTT

Position:

• chr2-214728537-C-CTT

Variant summary

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

The NM_000465.4(BARD1):​c.*138_*139insAA 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 0.51 (19363 hom., cov: 0)
  • Exomes 𝑓: 0.29 (527 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-C-CTT is Benign according to our data. Variant chr2-214728537-C-CTT is described in ClinVar as [Benign]. Clinvar id is 801873.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.58 is higher than 0.05.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.514 AC: 73918 AN: 143894 Hom.: 19356 Cov.: 0

Gnomad AFR AF: 0.587

Gnomad AMI AF: 0.487

Gnomad AMR AF: 0.446

Gnomad ASJ AF: 0.430

Gnomad EAS AF: 0.350

Gnomad SAS AF: 0.487

Gnomad FIN AF: 0.606

Gnomad MID AF: 0.419

Gnomad NFE AF: 0.495

Gnomad OTH AF: 0.473

GnomAD4 exome AF: 0.287 AC: 125700 AN: 438254 Hom.: 527 Cov.: 6 AF XY: 0.285 AC XY: 64799 AN XY: 227266

Gnomad4 AFR exome AF: 0.328

Gnomad4 AMR exome AF: 0.240

Gnomad4 ASJ exome AF: 0.263

Gnomad4 EAS exome AF: 0.207

Gnomad4 SAS exome AF: 0.272

Gnomad4 FIN exome AF: 0.350

Gnomad4 NFE exome AF: 0.293

Gnomad4 OTH exome AF: 0.287

GnomAD4 genome AF: 0.514 AC: 73926 AN: 143920 Hom.: 19363 Cov.: 0 AF XY: 0.516 AC XY: 35959 AN XY: 69624

Gnomad4 AFR AF: 0.587

Gnomad4 AMR AF: 0.445

Gnomad4 ASJ AF: 0.430

Gnomad4 EAS AF: 0.350

Gnomad4 SAS AF: 0.488

Gnomad4 FIN AF: 0.606

Gnomad4 NFE AF: 0.495

Gnomad4 OTH AF: 0.475

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 14, 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

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;