NM_000059.4(BRCA2):c.4965del (p.Cys1654_Tyr1655insTer) AND Hereditary cancer-predisposing syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Feb 12, 2024
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV004018932.1

Allele description [Variation Report for NM_000059.4(BRCA2):c.4965del (p.Cys1654_Tyr1655insTer)]

NM_000059.4(BRCA2):c.4965del (p.Cys1654_Tyr1655insTer)

Gene:

BRCA2:BRCA2 DNA repair associated [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

13q13.1

Genomic location:

Preferred name:

NM_000059.4(BRCA2):c.4965del (p.Cys1654_Tyr1655insTer)

HGVS:

NC_000013.11:g.32339320del
NG_012772.3:g.28841del
NM_000059.4:c.4965delMANE SELECT
NP_000050.3:p.Cys1654_Tyr1655insTer
LRG_293:g.28841del
NC_000013.10:g.32913457del
NC_000013.10:g.32913457delC
NM_000059.3:c.4965delC
U43746.1:n.5193delC

Nucleotide change:

5193delC

Links:

Breast Cancer Information Core (BIC) (BRCA2): 5193&base_change=del C; dbSNP: rs80359475

NCBI 1000 Genomes Browser:

rs80359475

Molecular consequence:

NM_000059.4:c.4965del - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Hereditary cancer-predisposing syndrome
Synonyms:: Neoplastic Syndromes, Hereditary; Tumor predisposition; Hereditary neoplastic syndrome; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV005027564	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Feb 12, 2024)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 21709188, 31742824, 35171259 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV005027564

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Feb 12, 2024)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Secondary somatic mutations restoring BRCA1/2 predict chemotherapy resistance in hereditary ovarian carcinomas.

Norquist B, Wurz KA, Pennil CC, Garcia R, Gross J, Sakai W, Karlan BY, Taniguchi T, Swisher EM.

J Clin Oncol. 2011 Aug 1;29(22):3008-15. doi: 10.1200/JCO.2010.34.2980. Epub 2011 Jun 27.

PubMed [citation]

PMID:: 21709188
PMCID:: PMC3157963

Prevalence of hereditary breast and ovarian cancer (HBOC) predisposition gene mutations among 882 HBOC high-risk Chinese individuals.

Shao D, Cheng S, Guo F, Zhu C, Yuan Y, Hu K, Wang Z, Meng X, Jin X, Xiong Y, Chai X, Li H, Zhang Y, Zhang H, Liu J, Ye M.

Cancer Sci. 2020 Feb;111(2):647-657. doi: 10.1111/cas.14242. Epub 2019 Dec 31.

PubMed [citation]

PMID:: 31742824
PMCID:: PMC7004523

See all PubMed Citations (3)

Details of each submission

From Ambry Genetics, SCV005027564.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

The c.4965delC pathogenic mutation, located in coding exon 10 of the BRCA2 gene, results from a deletion of one nucleotide at nucleotide position 4965, causing a translational frameshift with a predicted alternate stop codon (p.Y1655*). This alteration was identified in an individual diagnosed with pancreatic cancer (Yin L et al. JAMA Netw Open, 2022 Feb;5:e2148721). This variant was also identified in multiple individuals with a personal and/or family history of breast and/or ovarian cancer (Norquist B et al. J Clin Oncol, 2011 Aug;29:3008-15; Shao D et al. Cancer Sci, 2020 Feb;111:647-657). Of note, this alteration is also known as 5193delC 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.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: May 16, 2025

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