rs11571836

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000614259.2(BRCA2):n.*2847A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 196,350 control chromosomes in the GnomAD database, including 4,599 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★★).

Frequency

Genomes: 𝑓 0.19 ( 3037 hom., cov: 32)

Exomes 𝑓: 0.24 ( 1562 hom. )

Consequence

BRCA2
ENST00000614259.2 non_coding_transcript_exon

Scores

Clinical Significance

Benign reviewed by expert panel B:5

Conservation

PhyloP100: 0.315

Publications

26 publications found

Variant links:

Genes affected

BRCA2 (HGNC:1101): (BRCA2 DNA repair associated) Inherited mutations in BRCA1 and this gene, BRCA2, confer increased lifetime risk of developing breast or ovarian cancer. Both BRCA1 and BRCA2 are involved in maintenance of genome stability, specifically the homologous recombination pathway for double-strand DNA repair. The largest exon in both genes is exon 11, which harbors the most important and frequent mutations in breast cancer patients. The BRCA2 gene was found on chromosome 13q12.3 in human. The BRCA2 protein contains several copies of a 70 aa motif called the BRC motif, and these motifs mediate binding to the RAD51 recombinase which functions in DNA repair. BRCA2 is considered a tumor suppressor gene, as tumors with BRCA2 mutations generally exhibit loss of heterozygosity (LOH) of the wild-type allele. [provided by RefSeq, May 2020]

BRCA2 Gene-Disease associations (from GenCC):

breast-ovarian cancer, familial, susceptibility to, 2
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), ClinGen
Fanconi anemia complementation group D1
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen, G2P
pancreatic cancer, susceptibility to, 2
Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
sarcoma
Inheritance: AD Classification: MODERATE Submitted by: Genomics England PanelApp
hereditary breast ovarian cancer syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Fanconi anemia
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
medulloblastoma
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

BRCA2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 13-32399302-A-G is Benign according to our data. Variant chr13-32399302-A-G is described in ClinVar as Benign. ClinVar VariationId is 209928.Status of the report is reviewed_by_expert_panel, 3 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.38 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BRCA2	NM_000059.4 link	c.*532A>G		3_prime_UTR_variant	Exon 27 of 27	ENST00000380152.8	NP_000050.3	P51587

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
BRCA2	ENST00000614259.2 link	n.*2847A>G	non_coding_transcript_exon_variant	Exon 26 of 26	2		ENSP00000506251.1	A0A7P0TAP7
BRCA2	ENST00000380152.8 link	c.*532A>G	3_prime_UTR_variant	Exon 27 of 27	5	NM_000059.4	ENSP00000369497.3	P51587
BRCA2	ENST00000530893.7 link	c.*532A>G	3_prime_UTR_variant	Exon 27 of 27	1		ENSP00000499438.2	A0A590UJI7
BRCA2	ENST00000614259.2 link	n.*2847A>G	3_prime_UTR_variant	Exon 26 of 26	2		ENSP00000506251.1	A0A7P0TAP7

Frequencies

GnomAD3 genomes

AF:

0.190

AC:

28849

AN:

152008

Hom.:

3039

Cov.:

show subpopulations

Gnomad AFR

AF:

0.106

Gnomad AMI

AF:

0.127

Gnomad AMR

AF:

0.173

Gnomad ASJ

AF:

0.213

Gnomad EAS

AF:

0.395

Gnomad SAS

AF:

0.221

Gnomad FIN

AF:

0.238

Gnomad MID

AF:

0.237

Gnomad NFE

AF:

0.218

Gnomad OTH

AF:

0.206

GnomAD4 exome

AF:

0.243

AC:

10763

AN:

44224

Hom.:

1562

Cov.:

AF XY:

0.246

AC XY:

5042

AN XY:

20482

show subpopulations

African (AFR)

AF:

0.111

AC:

213

AN:

1912

American (AMR)

AF:

0.160

AC:

187

AN:

1166

Ashkenazi Jewish (ASJ)

AF:

0.223

AC:

609

AN:

2734

East Asian (EAS)

AF:

0.460

AC:

3294

AN:

7162

South Asian (SAS)

AF:

0.178

AC:

AN:

370

European-Finnish (FIN)

AF:

0.118

AC:

AN:

Middle Eastern (MID)

AF:

0.178

AC:

AN:

276

European-Non Finnish (NFE)

AF:

0.207

AC:

5573

AN:

26914

Other (OTH)

AF:

0.210

AC:

768

AN:

3656

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

364

728

1091

1455

1819

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

104

156

208

260

<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:

0.190

AC:

28841

AN:

152126

Hom.:

3037

Cov.:

AF XY:

0.194

AC XY:

14437

AN XY:

74378

show subpopulations

African (AFR)

AF:

0.106

AC:

4411

AN:

41538

American (AMR)

AF:

0.173

AC:

2641

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.213

AC:

738

AN:

3470

East Asian (EAS)

AF:

0.394

AC:

2036

AN:

5164

South Asian (SAS)

AF:

0.220

AC:

1059

AN:

4822

European-Finnish (FIN)

AF:

0.238

AC:

2519

AN:

10570

Middle Eastern (MID)

AF:

0.238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.218

AC:

14821

AN:

67964

Other (OTH)

AF:

0.204

AC:

430

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1178

2355

3533

4710

5888

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

320

640

960

1280

1600

<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:

0.202

Hom.:

4775

Bravo

AF:

0.182

Asia WGS

AF:

0.250

AC:

870

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: reviewed by expert panel

LINK: link

Submissions by phenotype

Breast-ovarian cancer, familial, susceptibility to, 2

Benign:2

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Jan 12, 2015

Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)

Significance:Benign

Review Status:reviewed by expert panel

Collection Method:curation

Class 1 not pathogenic based on frequency >1% in an outbred sampleset. Frequency 0.3811 (Asian), 0.04675 (African), 0.2177 (European), derived from 1000 genomes (2012-04-30). -

not provided

Benign:2

Jul 14, 2020

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 23299404) -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Fanconi anemia complementation group D1

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

4.6

(source)

DANN

Benign

0.80

PhyloP100

0.32

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

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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