2-214728537-CTTTTTT-CTTTTTTTT

Variant names:

• chr2-214728537-C-CTT
• rs113789798
• ENST00000471590.5:n.806_807dupAA

Variant summary

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

The ENST00000471590.5(BARD1):​n.806_807dupAA variant causes a non coding transcript exon 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 ENST00000471590.5 non_coding_transcript_exon
• 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-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 rank	MANE	Protein	UniProt
BARD1	NM_000465.4	c.*137_*138dupAA		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.*137_*138dupAA		3_prime_UTR_variant	Exon 11 of 11	1	NM_000465.4	ENSP00000260947.4

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

African (AFR) AF: 0.328 AC: 3799 AN: 11572

American (AMR) AF: 0.240 AC: 3541 AN: 14774

Ashkenazi Jewish (ASJ) AF: 0.263 AC: 3199 AN: 12152

East Asian (EAS) AF: 0.207 AC: 5557 AN: 26892

South Asian (SAS) AF: 0.272 AC: 9080 AN: 33382

European-Finnish (FIN) AF: 0.350 AC: 8514 AN: 24292

Middle Eastern (MID) AF: 0.228 AC: 519 AN: 2280

European-Non Finnish (NFE) AF: 0.293 AC: 84642 AN: 289050

Other (OTH) AF: 0.287 AC: 6849 AN: 23860

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

African (AFR) AF: 0.587 AC: 23096 AN: 39376

American (AMR) AF: 0.445 AC: 6481 AN: 14556

Ashkenazi Jewish (ASJ) AF: 0.430 AC: 1469 AN: 3418

East Asian (EAS) AF: 0.350 AC: 1745 AN: 4982

South Asian (SAS) AF: 0.488 AC: 2225 AN: 4564

European-Finnish (FIN) AF: 0.606 AC: 4664 AN: 7700

Middle Eastern (MID) AF: 0.427 AC: 122 AN: 286

European-Non Finnish (NFE) AF: 0.495 AC: 32742 AN: 66152

Other (OTH) AF: 0.475 AC: 942 AN: 1982

Alfa AF: 0.522 Hom.: 739

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Aug 14, 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

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs113789798; hg19: chr2-215593261;