2-214728537-CT-C

Variant names:

• chr2-214728537-CT-C
• rs113789798
• ENST00000471590.5:n.807delA

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_000465.4(BARD1):​c.*138delA 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
• Publications: 1 publications found

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]

BARD1 Gene-Disease associations (from GenCC):

• breast cancer

  Inheritance: AD Classification: DEFINITIVE Submitted by: G2P
• hereditary breast carcinoma

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen
• familial ovarian cancer

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen
• hereditary nonpolyposis colon cancer

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
BARD1	NM_000465.4	c.*138delA		3_prime_UTR_variant	Exon 11 of 11	ENST00000260947.9	NP_000456.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BARD1	ENST00000260947.9	c.*138delA		3_prime_UTR_variant	Exon 11 of 11	1	NM_000465.4	ENSP00000260947.4

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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.146 AC: 1704 AN: 11666

American (AMR) AF: 0.0788 AC: 1140 AN: 14470

Ashkenazi Jewish (ASJ) AF: 0.0824 AC: 983 AN: 11932

East Asian (EAS) AF: 0.0333 AC: 863 AN: 25916

South Asian (SAS) AF: 0.0601 AC: 1966 AN: 32710

European-Finnish (FIN) AF: 0.0453 AC: 1076 AN: 23756

Middle Eastern (MID) AF: 0.0929 AC: 209 AN: 2250

European-Non Finnish (NFE) AF: 0.0810 AC: 23121 AN: 285454

Other (OTH) AF: 0.0847 AC: 1997 AN: 23586

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

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

African (AFR) AF: 0.133 AC: 5261 AN: 39426

American (AMR) AF: 0.0439 AC: 639 AN: 14556

Ashkenazi Jewish (ASJ) AF: 0.0579 AC: 198 AN: 3420

East Asian (EAS) AF: 0.000201 AC: 1 AN: 4986

South Asian (SAS) AF: 0.0136 AC: 62 AN: 4568

European-Finnish (FIN) AF: 0.0216 AC: 166 AN: 7668

Middle Eastern (MID) AF: 0.0669 AC: 19 AN: 284

European-Non Finnish (NFE) AF: 0.0495 AC: 3275 AN: 66166

Other (OTH) AF: 0.0631 AC: 125 AN: 1980

Alfa AF: 0.0332 Hom.: 739

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Aug 09, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Familial cancer of breast Benign:1

May 28, 2019

Mendelics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.39
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs113789798; hg19: chr2-215593261;