13-32340072-ACTCT-ACT

Variant names:

• chr13-32340072-ACT-A
• rs80359530
• NM_000059.4:c.5722_5723delCT

Variant summary

Our verdict is Pathogenic. Variant got 16 ACMG points: 16P and 0B. PVS1 PP5_Very_Strong

The NM_000059.4(BRCA2):​c.5722_5723delCT​(p.Leu1908ArgfsTer2) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000151 in 1,461,602 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★★★). Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000015 (0 hom.)
• Consequence: BRCA2 NM_000059.4 frameshift
• Clinical Significance: Pathogenic reviewed by expert panel P:42
• Conservation: PhyloP100: 0.124

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]

ACMG classification

Verdict is Pathogenic. Variant got 16 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PP5: Variant 13-32340072-ACT-A is Pathogenic according to our data. Variant chr13-32340072-ACT-A is described in ClinVar as [Pathogenic]. Clinvar id is 9320.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr13-32340072-ACT-A is described in Lovd as [Pathogenic]. Variant chr13-32340072-ACT-A is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BRCA2	NM_000059.4	c.5722_5723delCT	p.Leu1908ArgfsTer2	frameshift_variant	Exon 11 of 27	ENST00000380152.8	NP_000050.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BRCA2	ENST00000380152.8	c.5722_5723delCT	p.Leu1908ArgfsTer2	frameshift_variant	Exon 11 of 27	5	NM_000059.4	ENSP00000369497.3
BRCA2	ENST00000530893.7	c.5353_5354delCT	p.Leu1785ArgfsTer2	frameshift_variant	Exon 11 of 27	1		ENSP00000499438.2
BRCA2	ENST00000614259.2	n.5722_5723delCT		non_coding_transcript_exon_variant	Exon 10 of 26	2		ENSP00000506251.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000399 AC: 1 AN: 250888 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135674

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000151 AC: 22 AN: 1461602 Hom.: 0 AF XY: 0.0000151 AC XY: 11 AN XY: 727094

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000153

Gnomad4 OTH exome AF: 0.0000331

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:42

Revision: reviewed by expert panel

Submissions by phenotype

Breast-ovarian cancer, familial, susceptibility to, 2 Pathogenic:14

Dec 21, 1995

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Jul 02, 2024

Department of Human Genetics, Hannover Medical School

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 27, 2015

Counsyl

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Oct 12, 2018

Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This c.5722_5723del (p.Leu1908Argfs*2) variant in the BRCA2 gene is predicted to introduce a premature translation termination codon. This variant has been reported in multiple unrelated individuals with breast cancer or ovarian cancer (PMID 8524414, 20927582, 21324516, 24010542, 25863477, 27553291), pancreatic cancer (PMID 25940717) and prostate cancer (PMID 20736950). This variant is extremely rare in general population database. Therefore, this c.5722_5723del (p.Leu1908Argfs*2) variant in the BRCA2 gene is classified as pathogenic. -

Oct 02, 2015

Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 29, 2002

Breast Cancer Information Core (BIC) (BRCA2)

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Nov 03, 2014

Michigan Medical Genetics Laboratories, University of Michigan

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 01, 2015

Department of Medical Genetics, Oslo University Hospital

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

University of Science and Technology Houari Boumediene, Laboratory of Molecular and Cellular Biology (LBCM)

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 27, 2024

Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

PVS1; PM5_PTC_Strong -

Mar 28, 2013

Sharing Clinical Reports Project (SCRP)

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Aug 14, 2024

Molecular Genetics and NGS Laboratory, Hospital Fundacion Valle Del Lili

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Null variant (frame-shift) in gene BRCA2, predicted to cause NMD. Loss-of-function is a known mechanism of disease. The exon affects 1 functional domain: UniProt protein BRCA2_HUMAN region of interest 'Interaction with RAD51'.The truncated region contains 2 405 pathogenic variants (PVS1). Combined evidence strength is Very Strong (score = 12).Very Strong: ClinVar classifies this variant as Pathogenic, 3 starsStrong: LOVD classifies this variant as Pathogenic (PP5). Variant not found in gnomAD genomes, GnomAD exomes homozygous allele count = 0 is less than 2 for AD/AR gene BRCA2, (PM2).We identified this variant in a 48-year-old patient diagnosed with triple-negative breast cancer. -

Apr 22, 2016

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

Significance: Pathogenic

Review Status: reviewed by expert panel

Collection Method: curation

Variant allele predicted to encode a truncated non-functional protein. -

Aug 26, 2022

BRCAlab, Lund University

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided Pathogenic:11

Oct 23, 2020

Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 04, 2015

Eurofins Ntd Llc (ga)

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Apr 28, 2022

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The BRCA2 c.5722_5723delCT; p.Leu1908ArgfsTer2 variant (rs80359530), also known as 5950delCT, has been described in several individuals and families affected with breast, ovarian, prostate, or pancreatic cancers (Cherbal 2010, de Juan 2015, Ding 2011, Edwards 2010, Holter 2015, Kwong 2009, Thompson 2012, Zhang 2011). This variant is reported in ClinVar (Variation ID: 9320) and is classified as pathogenic by an expert panel. This variant is only observed on one allele in the Genome Aggregation Database, indicating it is not a common polymorphism. This variant causes a frameshift by deleting 2 nucleotides, so it is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Based on available information, this variant is considered pathogenic. REFERENCES Cherbal F et al. BRCA1 and BRCA2 germline mutations screening in Algerian breast/ovarian cancer families. Dis Markers. 2010;28(6):377-84. PMID: 20683152. de Juan I et al. BRCA1 and BRCA2 mutations in males with familial breast and ovarian cancer syndrome. Results of a Spanish multicenter study. Fam Cancer. 2015 Dec;14(4):505-13. PMID: 26026974. Ding Y et al. Mutations in BRCA2 and PALB2 in male breast cancer cases from the United States. Breast Cancer Res Treat. 2011 Apr;126(3):771-8. PMID: 20927582. Edwards S et al. Prostate cancer in BRCA2 germline mutation carriers is associated with poorer prognosis. Br J Cancer. 2010 Sep 7;103(6):918-24. PMID: 20736950. Holter S et al. Germline BRCA Mutations in a Large Clinic-Based Cohort of Patients With Pancreatic Adenocarcinoma. J Clin Oncol. 2015 Oct 1;33(28):3124-9. PMID: 25940717. Kwong A et al. A BRCA2 founder mutation and seven novel deleterious BRCA mutations in southern Chinese women with breast and ovarian cancer. Breast Cancer Res Treat. 2009 Oct;117(3):683-6. PMID: 19353265. Thompson E et al. Exome sequencing identifies rare deleterious mutations in DNA repair genes FANCC and BLM as potential breast cancer susceptibility alleles. PLoS Genet. 2012 Sep;8(9):e1002894. PMID: 23028338. Zhang S et al. Frequencies of BRCA1 and BRCA2 mutations among 1,342 unselected patients with invasive ovarian cancer. Gynecol Oncol. 2011 May 1;121(2):353-7. PMID: 21324516. -

Dec 01, 2019

GeneDx

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Observed in individuals with a personal or family history consistent with pathogenic variants in this gene (Wooster 1995, Frank 1998, Couch 2007, Cherbal 2010, de Juan 2015, Holter 2015, Johns 2017, Pritzlaff 2017); Not observed at a significant frequency in large population cohorts (Lek 2016); Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; Also known as c.5950delCT; This variant is associated with the following publications: (PMID: 21324516, 20736950, 25136594, 17301269, 19353265, 28008555, 27553291, 29339979, 29335924, 29752822, 22535016, 20683152, 12181777, 26026974, 24830819, 23028338, 9667259, 17453335, 20104584, 22798144, 16835750, 12112655, 12048272, 14973102, 25863477, 8524414, 25940717, 27836010, 26843898, 25330149, 28454591, 27989354, 29470806, 28724667, 30720863, 30940775, 30078507, 30287823, 30720243, 30702160, 31528241, 31577767, 31447099, 31980526) -

Mar 04, 2025

Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Apr 18, 2019

Clinical Genetics and Genomics, Karolinska University Hospital

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Oct 24, 2023

Revvity Omics, Revvity

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Department of Pathology and Laboratory Medicine, Sinai Health System

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: clinical testing

The p.Leu1908ArgfsX2 deletion variant has been previously reported in the literature in at least 4 of 3460 proband chromosomes in individuals with hereditary breast, ovarian or pancreatic cancer and was shown to segregate with disease in one family (Selected publications: Edwards 2010, Heidemann 2012, Kwong 2009, Zhang 2011). In addition, it was reported 17x in the UMD database as causal and 42X in the BIC database as having clinical importance. This DNA alteration leads to a premature stop codon at position 1908, which is predicted to lead to a truncated or absent protein and loss of function. Loss of function variants of the BRCA2 gene are an established mechanism of disease in hereditary breast and ovarian cancer. In summary, this variant is classified as pathogenic. -

Feb 28, 2023

Clinical Genetics Laboratory, Skane University Hospital Lund

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jun 12, 2023

Quest Diagnostics Nichols Institute San Juan Capistrano

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The BRCA2 c.5722_5723del (p.Leu1908Argfs*2) variant alters the translational reading frame of the BRCA2 mRNA and causes the premature termination of BRCA2 protein synthesis. This variant has been reported in the published literature in individuals with breast and/or ovarian cancer (PMID: 30940775 (2019), 32341426 (2020), 34290354 (2021)), including male individuals with breast cancer (PMID: 20927582 (2011), 23028338 (2012)). This variant has also been reported in individuals with prostate cancer (PMID: 20736950 (2010)), and pancreatic cancer (PMID: 25940717 (2015), 31577767 (2019)). The frequency of this variant in the general population, 0.000004 (1/250888 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is consistent with pathogenicity. Based on the available information, this variant is classified as pathogenic. -

Feb 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

BRCA2: PVS1, PS4:Moderate, PM2:Supporting -

Hereditary breast ovarian cancer syndrome Pathogenic:4

Nov 23, 2022

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The p.Leu1908ArgfsX2 variant in BRCA2 has been reported in >60 individuals with BRCA2-associated cancers (Kwong 2009 PMID: 19353265, Cherbal 2010 PMID: 20683152, Zhang 2011, Edwards 2010 PMID: 20736950, Rebbeck 2018 PMID: 29446198, Breast Cancer Information Core (BIC) database). It has also been identified in 0.003% (1/30598) of South Asian chromosomes by gnomAD (http://gnomad.broadinstitute.org); however, this frequency is low enough to be consistent with the frequency of hereditary breast and ovarian cancer (HBOC) in the general population. This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 1908 and leads to a premature termination codon 2 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Heterozygous loss of function of the BRCA2 gene is an established disease mechanism in HBOC. Additionally, this variant was classified as pathogenic on April 22, 2016 by the ClinGen-approved ENIGMA expert panel (Variation ID 9320). In summary, this variant meets criteria to be classified as pathogenic for autosomal dominant HBOC. ACMG/AMP criteria applied: PVS1, PS4, PM2_Supporting. -

Jan 22, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This sequence change creates a premature translational stop signal (p.Leu1908Argfs*2) in the BRCA2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). This variant is present in population databases (rs80359530, gnomAD 0.003%). This premature translational stop signal has been observed in individual(s) with breast cancer (PMID: 8524414, 20736950, 20927582, 21324516, 22535016, 23028338, 24963353, 25940717, 27553291). It has also been observed to segregate with disease in related individuals. This variant is also known as 5950delCT. For these reasons, this variant has been classified as Pathogenic. -

Jan 31, 2014

Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: research

- -

Apr 02, 2021

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant summary: BRCA2 c.5722_5723delCT (p.Leu1908ArgfsX2) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 4e-06 in 250888 control chromosomes. c.5722_5723delCT has been reported in the literature in multiple individuals affected with Hereditary Breast And Ovarian Cancer Syndrome (example, Rebbeck_2018). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Multiple clinical diagnostic laboratories, an expert panel (ENIGMA) and a consortium (CIMBA) have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All submitters classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. -

Hereditary cancer-predisposing syndrome Pathogenic:3

Feb 21, 2022

Ambry Genetics

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.5722_5723delCT pathogenic mutation, located in coding exon 10 of the BRCA2 gene, results from a deletion of two nucleotides at nucleotide positions 5722 to 5723, causing a translational frameshift with a predicted alternate stop codon (p.L1908Rfs*2). This mutation has been reported in multiple hereditary breast and ovarian cancer (HBOC) syndrome cohorts, including individuals with male breast cancer, pancreatic cancer and prostate cancer (Wooster R et al. Nature. 1995 Dec;378:789-92; Edwards SM et al. Br. J. Cancer. 2010 Sep;103:918-24; Cherbal F et al. Dis Markers, 2010;28:377-84; Ding YC et al. Breast Cancer Res. Treat. 2011 Apr;126:771-8; Zhang S et al. Gynecol. Oncol. 2011 May;121(2):353-7; Konstantopoulou I et al. Clin. Genet. 2014 Jan;85:36-42; Johns AL et al. Genome Med. 2014 May;6:42; Ruiz A et al. Biomed Res Int. 2014 Jun;2014:542541; Kang E et al. Breast Cancer Res. Treat. 2015 May;151:157-68; Holter S et al. J. Clin. Oncol. 2015 Oct;33:3124-9; de Juan I et al. Fam. Cancer. 2015 Dec;14:505-13; Rashid MU et al. BMC Cancer. 2016 08;16:673; Na R et al. Eur Urol, 2017 05;71:740-747; Sun J et al. Clin. Cancer Res. 2017 Oct;23:6113-6119; Singh J et al. Breast Cancer Res Treat, 2018 Jul;170:189-196; Momozowa Y et al. Nat Commun. 2018 10;9(1):4083; Wang H et al. Medicine (Baltimore), 2019 Oct;98:e17443; Guo Y et al. Biosci Rep, 2019 04;39; Deng M et al. Int J Cancer, 2019 09;145:1517-1528; De Talhouet S et al. Sci Rep, 2020 04;10:7073; Shao D et al. Cancer Sci, 2020 Feb;111:647-657; Abdel-Razeq H et al. Sci Rep, 2021 07;11:14906). Of note, this mutation is also designated as 5950delCT and c.5718_5719del in published literature. In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. -

Apr 04, 2023

Color Diagnostics, LLC DBA Color Health

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant deletes 2 nucleotides in exon 11 of the BRCA2 gene, creating a frameshift and premature translation stop signal. This variant is also known as 5950delCT, 5946delCT and 5950-5951delCT in the literature. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in at least 12 individuals affected with breast and/or ovarian cancer (PMID: 8665505, 14647210, 19353265, 20683152, 21324516, 24010542, 25136594, 26026974, 27553291, 28724667, 29470806, 30287823, 33471991; Leiden Open Variation Database DB-ID BRCA2_001607) and five individuals affected with pancreatic cancer (PMID: 24963353, 25940717) or prostate cancer (PMID: 20736950, 31214711). This variant also has been reported in families suspected of being affected with hereditary breast and ovarian cancer (PMID: 8524414, 11802209, 15340362, 16234499, 25863477). This variant has been identified in 1/250888 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Loss of BRCA2 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic. -

Feb 16, 2022

Sema4, Sema4

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: curation

- -

Familial cancer of breast Pathogenic:3

Mar 21, 2024

Baylor Genetics

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Center for Precision Medicine, Meizhou People's Hospital

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Oct 25, 2022

Eurofins-Biomnis

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breast and/or ovarian cancer Pathogenic:2

May 15, 2015

Foulkes Cancer Genetics LDI, Lady Davis Institute for Medical Research

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jun 23, 2023

CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Medulloblastoma;C0346153:Familial cancer of breast;C1838457:Fanconi anemia complementation group D1;C2675520:Breast-ovarian cancer, familial, susceptibility to, 2;C2751641:Glioma susceptibility 3;C2931456:Familial prostate cancer;C3150546:Pancreatic cancer, susceptibility to, 2;CN033288:Wilms tumor 1 Pathogenic:2

-

Juno Genomics, Hangzhou Juno Genomics, Inc

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

PVS1+PM5_Strong（PTC） -

May 10, 2024

Fulgent Genetics, Fulgent Genetics

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breast-ovarian cancer, familial, susceptibility to, 1 Pathogenic:1

Apr 02, 2020

Department of Molecular Diagnostics, Institute of Oncology Ljubljana

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

BRCA2-related cancer predisposition Pathogenic:1

Sep 27, 2024

All of Us Research Program, National Institutes of Health

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant deletes 2 nucleotides in exon 11 of the BRCA2 gene, creating a frameshift and premature translation stop signal. This variant is also known as 5950delCT, 5946delCT and 5950-5951delCT in the literature. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in at least 12 individuals affected with breast and/or ovarian cancer (PMID: 8665505, 14647210, 19353265, 20683152, 21324516, 24010542, 25136594, 26026974, 27553291, 28724667, 29470806, 30287823, 33471991; Leiden Open Variation Database DB-ID BRCA2_001607) and five individuals affected with pancreatic cancer (PMID: 24963353, 25940717) or prostate cancer (PMID: 20736950, 31214711). This variant also has been reported in families suspected of being affected with hereditary breast and ovarian cancer (PMID: 8524414, 11802209, 15340362, 16234499, 25863477). This variant has been identified in 1/250888 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Loss of BRCA2 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic. -

Gastric cancer Pathogenic:1

Jul 01, 2021

Laboratory for Genotyping Development, RIKEN

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: research

- -

Computational scores

Source: dbNSFP v4.3

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

LitVar

Other links and lift over

dbSNP: rs80359530; hg19: chr13-32914209;