2-214792458-TAAAAA-TAAA

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP6BA1

The NM_000465.4(BARD1):c.216-15_216-14delTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0839 in 1,359,760 control chromosomes in the GnomAD database, including 507 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.062 ( 223 hom., cov: 0)

Exomes 𝑓: 0.086 ( 284 hom. )

Consequence

BARD1
NM_000465.4 intron

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:4

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 -9 ACMG points.

BP6

Variant 2-214792458-TAA-T is Benign according to our data. Variant chr2-214792458-TAA-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 334196.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0904 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000465.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
BARD1	NM_000465.4	MANE Select	c.216-15_216-14delTT	intron	N/A	NP_000456.2
BARD1	NM_001282543.2		c.159-15_159-14delTT	intron	N/A	NP_001269472.1
BARD1	NM_001282545.2		c.215+4601_215+4602delTT	intron	N/A	NP_001269474.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
BARD1	ENST00000260947.9	TSL:1 MANE Select	c.216-15_216-14delTT	intron	N/A	ENSP00000260947.4
BARD1	ENST00000617164.5	TSL:1	c.159-15_159-14delTT	intron	N/A	ENSP00000480470.1
BARD1	ENST00000613706.5	TSL:1	c.216-15_216-14delTT	intron	N/A	ENSP00000484976.2

Frequencies

GnomAD3 genomes

AF:

0.0617

AC:

7844

AN:

127182

Hom.:

217

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0529

Gnomad AMI

AF:

0.00783

Gnomad AMR

AF:

0.0938

Gnomad ASJ

AF:

0.0589

Gnomad EAS

AF:

0.000947

Gnomad SAS

AF:

0.0516

Gnomad FIN

AF:

0.0571

Gnomad MID

AF:

0.0692

Gnomad NFE

AF:

0.0659

Gnomad OTH

AF:

0.0666

GnomAD2 exomes

AF:

0.111

AC:

10714

AN:

96390

AF XY:

0.114

show subpopulations

Gnomad AFR exome

AF:

0.0986

Gnomad AMR exome

AF:

0.132

Gnomad ASJ exome

AF:

0.112

Gnomad EAS exome

AF:

0.0321

Gnomad FIN exome

AF:

0.0841

Gnomad NFE exome

AF:

0.119

Gnomad OTH exome

AF:

0.123

GnomAD4 exome

AF:

0.0862

AC:

106209

AN:

1232548

Hom.:

284

AF XY:

0.0862

AC XY:

52636

AN XY:

610506

show subpopulations

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

African (AFR)

AF:

0.0813

AC:

2114

AN:

26000

American (AMR)

AF:

0.123

AC:

2884

AN:

23466

Ashkenazi Jewish (ASJ)

AF:

0.0925

AC:

1988

AN:

21498

East Asian (EAS)

AF:

0.0282

AC:

911

AN:

32314

South Asian (SAS)

AF:

0.0932

AC:

6151

AN:

66018

European-Finnish (FIN)

AF:

0.0637

AC:

2380

AN:

37360

Middle Eastern (MID)

AF:

0.100

AC:

404

AN:

4026

European-Non Finnish (NFE)

AF:

0.0873

AC:

84743

AN:

971146

Other (OTH)

AF:

0.0914

AC:

4634

AN:

50720

⚠️ 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: 0.370

Heterozygous variant carriers

4313

8625

12938

17250

21563

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3160

6320

9480

12640

15800

<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:

0.0618

AC:

7861

AN:

127212

Hom.:

223

Cov.:

AF XY:

0.0624

AC XY:

3815

AN XY:

61134

show subpopulations

African (AFR)

AF:

0.0529

AC:

1823

AN:

34446

American (AMR)

AF:

0.0948

AC:

1236

AN:

13032

Ashkenazi Jewish (ASJ)

AF:

0.0589

AC:

181

AN:

3074

East Asian (EAS)

AF:

0.000950

AC:

AN:

4212

South Asian (SAS)

AF:

0.0521

AC:

214

AN:

4104

European-Finnish (FIN)

AF:

0.0571

AC:

373

AN:

6536

Middle Eastern (MID)

AF:

0.0720

AC:

AN:

236

European-Non Finnish (NFE)

AF:

0.0659

AC:

3892

AN:

59052

Other (OTH)

AF:

0.0656

AC:

115

AN:

1754

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

348

696

1043

1391

1739

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

172

258

344

430

<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:

0.0333

Hom.:

ClinVar

ClinVar submissions as Germline

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

Hereditary cancer-predisposing syndrome (2)

Breast neoplasm (1)

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.80

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over