2-214792458-TAAAAA-TAAAA

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_000465.4(BARD1):c.216-14delT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.32 ( 5418 hom., cov: 0)

Exomes 𝑓: 0.40 ( 2229 hom. )

Failed GnomAD Quality Control

Consequence

BARD1
NM_000465.4 intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: -0.884

Publications

4 publications found

Variant links:

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

BARD1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP6

Variant 2-214792458-TA-T is Benign according to our data. Variant chr2-214792458-TA-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 142007.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.343 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BARD1	NM_000465.4 link	c.216-14delT		intron_variant	Intron 2 of 10	ENST00000260947.9	NP_000456.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BARD1	ENST00000260947.9 link	c.216-14delT		intron_variant	Intron 2 of 10	1	NM_000465.4	ENSP00000260947.4

Frequencies

GnomAD3 genomes

AF:

0.316

AC:

40170

AN:

127116

Hom.:

5420

Cov.:

show subpopulations

Gnomad AFR

AF:

0.327

Gnomad AMI

AF:

0.344

Gnomad AMR

AF:

0.338

Gnomad ASJ

AF:

0.337

Gnomad EAS

AF:

0.239

Gnomad SAS

AF:

0.358

Gnomad FIN

AF:

0.199

Gnomad MID

AF:

0.323

Gnomad NFE

AF:

0.319

Gnomad OTH

AF:

0.333

GnomAD2 exomes

AF:

0.423

AC:

40761

AN:

96390

AF XY:

0.423

show subpopulations

Gnomad AFR exome

AF:

0.426

Gnomad AMR exome

AF:

0.416

Gnomad ASJ exome

AF:

0.431

Gnomad EAS exome

AF:

0.451

Gnomad FIN exome

AF:

0.403

Gnomad NFE exome

AF:

0.418

Gnomad OTH exome

AF:

0.425

GnomAD4 exome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.403

AC:

468747

AN:

1161964

Hom.:

2229

Cov.:

AF XY:

0.405

AC XY:

233202

AN XY:

575634

show subpopulations

African (AFR)

AF:

0.406

AC:

10026

AN:

24698

American (AMR)

AF:

0.388

AC:

8943

AN:

23042

Ashkenazi Jewish (ASJ)

AF:

0.413

AC:

8592

AN:

20820

East Asian (EAS)

AF:

0.435

AC:

12991

AN:

29854

South Asian (SAS)

AF:

0.416

AC:

26537

AN:

63722

European-Finnish (FIN)

AF:

0.359

AC:

12697

AN:

35382

Middle Eastern (MID)

AF:

0.383

AC:

1492

AN:

3894

European-Non Finnish (NFE)

AF:

0.403

AC:

368045

AN:

912378

Other (OTH)

AF:

0.403

AC:

19424

AN:

48174

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.400

Heterozygous variant carriers

15336

30672

46008

61344

76680

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14178

28356

42534

56712

70890

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.316

AC:

40170

AN:

127148

Hom.:

5418

Cov.:

AF XY:

0.312

AC XY:

19090

AN XY:

61092

show subpopulations

African (AFR)

AF:

0.326

AC:

11241

AN:

34432

American (AMR)

AF:

0.338

AC:

4395

AN:

13018

Ashkenazi Jewish (ASJ)

AF:

0.337

AC:

1035

AN:

3074

East Asian (EAS)

AF:

0.239

AC:

1005

AN:

4206

South Asian (SAS)

AF:

0.358

AC:

1468

AN:

4100

European-Finnish (FIN)

AF:

0.199

AC:

1304

AN:

6550

Middle Eastern (MID)

AF:

0.318

AC:

AN:

236

European-Non Finnish (NFE)

AF:

0.319

AC:

18807

AN:

59018

Other (OTH)

AF:

0.330

AC:

577

AN:

1750

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

1359

2718

4076

5435

6794

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

412

824

1236

1648

2060

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0746

Hom.:

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Hereditary cancer-predisposing syndrome

Benign:4

Apr 07, 2015

Color Diagnostics, LLC DBA Color Health

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Jan 31, 2014

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The variant is found in BR-OV-HEREDIC panel(s).

Oct 11, 2013

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Internal frequency is too high to be a pathogenic mutation based on disease/syndrome prevalence and penetrance

Jul 10, 2025

GeneKor MSA

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not specified

Benign:3

Mar 04, 2025

Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Familial cancer of breast

Benign:2

Jul 11, 2017

Department of Pathology and Laboratory Medicine, Sinai Health System

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Jul 19, 2024

Myriad Genetics, Inc.

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign. This variant is intronic and is not expected to impact mRNA splicing.

Breast neoplasm

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Malignant tumor of breast

Benign:1

Department of Pathology and Laboratory Medicine, Sinai Health System

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

The BARD1 c.216-14delT variant was not identified in the literature nor was it identified in the Cosmic, MutDB, Zhejiang Colon Cancer Database, NHLBI Exome Sequencing Project databases. The variant was identified in dbSNP (ID: rs56130510) as â€šÃ„ÃºWith Likely benign alleleâ€šÃ„Ã¹, ClinVar (classified benign by Ambry Genetics and GeneDx; and likely benign by Illumina), Clinvitae (2x), and in the 1000 Genomes Project at a frequency of 5%, as well as in HAPMAP-SAS in 488 of 978 chromosomes (frequency: 0.5)/-AMR in 334 of 694 chromosomes (frequency: 0.5)/-EUR in 442 of 1006 chromosomes (frequency: 0.4), and the Exome Aggregation Consortium (August 8th 2016) control database in 1 of 976 chromosomes (frequency 0.001). The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a difference in splicing. In summary, based on the above information this variant meets our laboratory's criteria to be classified as benign.

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.88

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over