rs11571651

Variant names:

Variant summary

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

The NM_000059.4(BRCA2):c.1910-51G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0416 in 1,549,260 control chromosomes in the GnomAD database, including 2,057 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★★).

Frequency

Genomes: 𝑓 0.041 ( 216 hom., cov: 32)

Exomes 𝑓: 0.042 ( 1841 hom. )

Consequence

BRCA2
NM_000059.4 intron

Scores

Clinical Significance

Benign reviewed by expert panel B:9

Conservation

PhyloP100: 0.0290

Publications

18 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):

BRCA2-related cancer predisposition
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
breast-ovarian cancer, familial, susceptibility to, 2
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
Fanconi anemia complementation group D1
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics
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=-0.82).

BP6

Variant 13-32336214-G-T is Benign according to our data. Variant chr13-32336214-G-T is described in ClinVar as Benign. ClinVar VariationId is 209688.Status of the report is reviewed_by_expert_panel, 3 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.106 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000059.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
BRCA2	NM_000059.4	MANE Select	c.1910-51G>T	intron	N/A	NP_000050.3	A0A7P0T9D7
BRCA2	NM_001432077.1		c.1910-51G>T	intron	N/A	NP_001419006.1	A0A7P0T9D7
BRCA2	NM_001406720.1		c.1910-51G>T	intron	N/A	NP_001393649.1	A0A8V8TPZ2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
BRCA2	ENST00000380152.8	TSL:5 MANE Select	c.1910-51G>T	intron	N/A	ENSP00000369497.3	P51587
BRCA2	ENST00000544455.6	TSL:1	c.1910-51G>T	intron	N/A	ENSP00000439902.1	P51587
BRCA2	ENST00000530893.7	TSL:1	c.1541-51G>T	intron	N/A	ENSP00000499438.2	A0A590UJI7

Frequencies

GnomAD3 genomes

AF:

0.0408

AC:

6210

AN:

152100

Hom.:

213

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0213

Gnomad AMI

AF:

0.0264

Gnomad AMR

AF:

0.0973

Gnomad ASJ

AF:

0.0435

Gnomad EAS

AF:

0.0988

Gnomad SAS

AF:

0.114

Gnomad FIN

AF:

0.0148

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.0344

Gnomad OTH

AF:

0.0465

GnomAD2 exomes

AF:

0.0506

AC:

10617

AN:

209908

AF XY:

0.0531

show subpopulations

Gnomad AFR exome

AF:

0.0224

Gnomad AMR exome

AF:

0.0724

Gnomad ASJ exome

AF:

0.0364

Gnomad EAS exome

AF:

0.101

Gnomad FIN exome

AF:

0.0156

Gnomad NFE exome

AF:

0.0339

Gnomad OTH exome

AF:

0.0497

GnomAD4 exome

AF:

0.0417

AC:

58223

AN:

1397042

Hom.:

1841

Cov.:

AF XY:

0.0441

AC XY:

30615

AN XY:

694330

show subpopulations

African (AFR)

AF:

0.0200

AC:

623

AN:

31208

American (AMR)

AF:

0.0760

AC:

2770

AN:

36466

Ashkenazi Jewish (ASJ)

AF:

0.0407

AC:

958

AN:

23526

East Asian (EAS)

AF:

0.119

AC:

4682

AN:

39382

South Asian (SAS)

AF:

0.114

AC:

8845

AN:

77550

European-Finnish (FIN)

AF:

0.0152

AC:

789

AN:

51964

Middle Eastern (MID)

AF:

0.0629

AC:

249

AN:

3956

European-Non Finnish (NFE)

AF:

0.0341

AC:

36675

AN:

1075214

Other (OTH)

AF:

0.0456

AC:

2632

AN:

57776

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

2791

5582

8373

11164

13955

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1502

3004

4506

6008

7510

<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:

0.0409

AC:

6229

AN:

152218

Hom.:

216

Cov.:

AF XY:

0.0436

AC XY:

3242

AN XY:

74414

show subpopulations

African (AFR)

AF:

0.0214

AC:

888

AN:

41542

American (AMR)

AF:

0.0980

AC:

1498

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.0435

AC:

151

AN:

3470

East Asian (EAS)

AF:

0.0986

AC:

510

AN:

5172

South Asian (SAS)

AF:

0.114

AC:

549

AN:

4818

European-Finnish (FIN)

AF:

0.0148

AC:

157

AN:

10614

Middle Eastern (MID)

AF:

0.0340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0344

AC:

2340

AN:

68008

Other (OTH)

AF:

0.0483

AC:

102

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

303

606

909

1212

1515

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

148

222

296

370

<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:

0.0354

Hom.:

Bravo

AF:

0.0422

Asia WGS

AF:

0.110

AC:

381

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:reviewed by expert panel

View on ClinVar

Pathogenic

VUS

Benign

Condition

Breast-ovarian cancer, familial, susceptibility to, 2 (3)

Hereditary cancer-predisposing syndrome (2)

not provided (2)

not specified (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

2.4

(source)

DANN

Benign

0.53

PhyloP100

0.029

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over