rs11571661

Variant names:

• chr13-32341273-CAATT-C
• rs11571661
• NM_000059.4:c.6841+80_6841+83delTTAA

Your query was ambiguous. Multiple possible variants found:

• chr13-32341273-CAATT-C
• chr13-32341273-CAATT-CAATTAATT

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_000059.4(BRCA2):​c.6841+80_6841+83delTTAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.304 in 1,594,908 control chromosomes in the GnomAD database, including 74,988 homozygotes. Variant has been reported in ClinVar as Benign (★★★).

• Frequency:
  • Genomes: 𝑓 0.28 (6125 hom., cov: 19)
  • Exomes 𝑓: 0.31 (68863 hom.)
• Consequence: BRCA2 NM_000059.4 intron
• Clinical Significance: Benign reviewed by expert panel U:2 B:7 O:1
• Conservation: PhyloP100: 0.759
• Publications: 11 publications found

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

ACMG classification

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

• BP6: Variant 13-32341273-CAATT-C is Benign according to our data. Variant chr13-32341273-CAATT-C is described in ClinVar as Benign. ClinVar VariationId is 126122.Status of the report is reviewed_by_expert_panel, 3 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.379 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BRCA2	NM_000059.4	c.6841+80_6841+83delTTAA		intron_variant	Intron 11 of 26	ENST00000380152.8	NP_000050.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BRCA2	ENST00000380152.8	c.6841+78_6841+81delAATT		intron_variant	Intron 11 of 26	5	NM_000059.4	ENSP00000369497.3
BRCA2	ENST00000530893.7	c.6472+78_6472+81delAATT		intron_variant	Intron 11 of 26	1		ENSP00000499438.2
BRCA2	ENST00000614259.2	n.6841+78_6841+81delAATT		intron_variant	Intron 10 of 25	2		ENSP00000506251.1

Frequencies

GnomAD3 genomes AF: 0.281 AC: 42671 AN: 151646 Hom.: 6128 Cov.: 19

Gnomad AFR AF: 0.229

Gnomad AMI AF: 0.176

Gnomad AMR AF: 0.222

Gnomad ASJ AF: 0.306

Gnomad EAS AF: 0.395

Gnomad SAS AF: 0.291

Gnomad FIN AF: 0.315

Gnomad MID AF: 0.295

Gnomad NFE AF: 0.313

Gnomad OTH AF: 0.275

GnomAD4 exome AF: 0.306 AC: 441481 AN: 1443142 Hom.: 68863 AF XY: 0.307 AC XY: 220348 AN XY: 718630

African (AFR) AF: 0.223 AC: 7367 AN: 33056

American (AMR) AF: 0.214 AC: 9568 AN: 44614

Ashkenazi Jewish (ASJ) AF: 0.305 AC: 7919 AN: 25984

East Asian (EAS) AF: 0.435 AC: 17155 AN: 39446

South Asian (SAS) AF: 0.298 AC: 25336 AN: 85080

European-Finnish (FIN) AF: 0.310 AC: 16413 AN: 53030

Middle Eastern (MID) AF: 0.255 AC: 1385 AN: 5432

European-Non Finnish (NFE) AF: 0.308 AC: 338336 AN: 1096776

Other (OTH) AF: 0.301 AC: 18002 AN: 59724

GnomAD4 genome AF: 0.281 AC: 42663 AN: 151766 Hom.: 6125 Cov.: 19 AF XY: 0.282 AC XY: 20942 AN XY: 74156

African (AFR) AF: 0.228 AC: 9459 AN: 41400

American (AMR) AF: 0.222 AC: 3389 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.306 AC: 1059 AN: 3464

East Asian (EAS) AF: 0.394 AC: 2026 AN: 5146

South Asian (SAS) AF: 0.288 AC: 1387 AN: 4808

European-Finnish (FIN) AF: 0.315 AC: 3311 AN: 10512

Middle Eastern (MID) AF: 0.291 AC: 85 AN: 292

European-Non Finnish (NFE) AF: 0.313 AC: 21216 AN: 67868

Other (OTH) AF: 0.271 AC: 571 AN: 2104

Alfa AF: 0.174 Hom.: 378

Bravo AF: 0.272

Asia WGS AF: 0.278 AC: 968 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Uncertain:2 Benign:7 Other:1

Revision: reviewed by expert panel

Submissions by phenotype

Breast-ovarian cancer, familial, susceptibility to, 2 Uncertain:1 Benign:3

Dec 17, 2010

Breast Cancer Information Core (BIC) (BRCA2)

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Dec 03, 2017

Genomic Research Center, Shahid Beheshti University of Medical Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Oct 09, 2014

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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 0.38 (Asian), 0.18 (African), 0.29 (European), derived from 1000 genomes (2012-04-30). -

not specified Uncertain:1 Benign:2

Apr 20, 2017

Department of Pathology and Molecular Medicine, Queen's University

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided Benign:1

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Hereditary cancer-predisposing syndrome Benign:1

Mar 10, 2015

Color Diagnostics, LLC DBA Color Health

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Familial cancer of breast Other:1

-

Genomic Research Center, Shahid Beheshti University of Medical Sciences

Significance: not provided

Review Status: no classification provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.76
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11571661; hg19: chr13-32915410; COSMIC: COSV101204050;