chr2-214792458-TAAA-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP6_Very_Strong

The NM_000465.4(BARD1):c.216-16_216-14delTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00175 in 1,396,112 control chromosomes in the GnomAD database, including 1 homozygotes. There is a variant allele frequency bias in the population database for this variant (GnomAd4), which may indicate mosaicism or somatic mutations in the reference population data. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.000071 ( 0 hom., cov: 0)

Exomes 𝑓: 0.0019 ( 1 hom. )

Consequence

BARD1
NM_000465.4 intron

Scores

Not classified

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.804

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 -8 ACMG points.

BP6

Variant 2-214792458-TAAA-T is Benign according to our data. Variant chr2-214792458-TAAA-T is described in ClinVar as Likely_benign. ClinVar VariationId is 490957.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BARD1	NM_000465.4 link	c.216-16_216-14delTTT		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.216-16_216-14delTTT		intron_variant	Intron 2 of 10	1	NM_000465.4	ENSP00000260947.4

Frequencies

GnomAD3 genomes

AF:

0.0000707

AC:

AN:

127240

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000291

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000230

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000305

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000338

Gnomad OTH

AF:

0.000574

GnomAD2 exomes

AF:

0.00582

AC:

561

AN:

96390

AF XY:

0.00612

show subpopulations

Gnomad AFR exome

AF:

0.00509

Gnomad AMR exome

AF:

0.00895

Gnomad ASJ exome

AF:

0.00397

Gnomad EAS exome

AF:

0.000601

Gnomad FIN exome

AF:

0.00628

Gnomad NFE exome

AF:

0.00594

Gnomad OTH exome

AF:

0.00551

GnomAD4 exome

AF:

0.00191

AC:

2428

AN:

1268842

Hom.:

AF XY:

0.00194

AC XY:

1219

AN XY:

628372

show subpopulations

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

African (AFR)

AF:

0.00198

AC:

AN:

26728

American (AMR)

AF:

0.00678

AC:

163

AN:

24058

Ashkenazi Jewish (ASJ)

AF:

0.00231

AC:

AN:

22122

East Asian (EAS)

AF:

0.000300

AC:

AN:

33312

South Asian (SAS)

AF:

0.00268

AC:

182

AN:

67978

European-Finnish (FIN)

AF:

0.00240

AC:

AN:

38298

Middle Eastern (MID)

AF:

0.00437

AC:

AN:

4118

European-Non Finnish (NFE)

AF:

0.00175

AC:

1747

AN:

999910

Other (OTH)

AF:

0.00214

AC:

112

AN:

52318

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.278

Heterozygous variant carriers

221

442

663

884

1105

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

150

200

250

<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:

0.0000707

AC:

AN:

127270

Hom.:

Cov.:

AF XY:

0.0000491

AC XY:

AN XY:

61158

show subpopulations

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

African (AFR)

AF:

0.0000290

AC:

AN:

34454

American (AMR)

AF:

0.000230

AC:

AN:

13042

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3076

East Asian (EAS)

AF:

0.00

AC:

AN:

4212

South Asian (SAS)

AF:

0.00

AC:

AN:

4104

European-Finnish (FIN)

AF:

0.000305

AC:

AN:

6550

Middle Eastern (MID)

AF:

0.00

AC:

AN:

236

European-Non Finnish (NFE)

AF:

0.0000339

AC:

AN:

59076

Other (OTH)

AF:

0.000570

AC:

AN:

1754

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.00589611), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.381

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 04, 2025

Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Hereditary cancer-predisposing syndrome

Benign:1

Jun 24, 2017

Color Diagnostics, LLC DBA Color Health

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.80

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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