NM_000059.4(BRCA2):c.1499del (p.Gly500fs) AND not provided

Germline classification:: Pathogenic (5 submissions)
Last evaluated:: May 19, 2025
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV001269907.30

Allele description [Variation Report for NM_000059.4(BRCA2):c.1499del (p.Gly500fs)]

NM_000059.4(BRCA2):c.1499del (p.Gly500fs)

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.1499del (p.Gly500fs)

HGVS:

NC_000013.10:g.32907112del
NC_000013.11:g.32332977del
NG_012772.3:g.22498del
NM_000059.4:c.1499delMANE SELECT
NP_000050.3:p.Gly500fs
LRG_293:g.22498del
NC_000013.10:g.32907112del
NC_000013.10:g.32907114del
NC_000013.10:g.32907114del
NC_000013.10:g.32907114delG
NM_000059.3:c.1499delG
p.Gly500ValfsX9

Nucleotide change:

1727delG

Links:

dbSNP: rs397507591

NCBI 1000 Genomes Browser:

rs397507591

Molecular consequence:

NM_000059.4:c.1499del - frameshift variant - [Sequence Ontology: SO:0001589]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001450262	Clinical Genetics and Genomics, Karolinska University Hospital	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Dec 11, 2014)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001470196	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Pathogenic (Dec 13, 2019)	unknown	clinical testing	PubMed (4) [See all records that cite these PMIDs] 30702160, 11802209, 19941162, 26467025
SCV001905529	Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Sep 15, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002820717	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (May 19, 2025)	germline	clinical testing	Citation Link,
SCV002822064	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Pathogenic (Aug 1, 2023)	germline	clinical testing	Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	11	not provided	not provided	1	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Germline variation in BRCA1/2 is highly ethnic-specific: Evidence from over 30,000 Chinese hereditary breast and ovarian cancer patients.

Bhaskaran SP, Chandratre K, Gupta H, Zhang L, Wang X, Cui J, Kim YC, Sinha S, Jiang L, Lu B, Wu X, Qin Z, Huang T, Wang SM.

Int J Cancer. 2019 Aug 15;145(4):962-973. doi: 10.1002/ijc.32176. Epub 2019 Feb 13.

PubMed [citation]

PMID:: 30702160
PMCID:: PMC6617753

Comprehensive analysis of 989 patients with breast or ovarian cancer provides BRCA1 and BRCA2 mutation profiles and frequencies for the German population.

Meindl A; German Consortium for Hereditary Breast and Ovarian Cancer.

Int J Cancer. 2002 Feb 1;97(4):472-80.

PubMed [citation]

PMID:: 11802209

See all PubMed Citations (5)

Details of each submission

From Clinical Genetics and Genomics, Karolinska University Hospital, SCV001450262.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	5	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		5	not provided	not provided	not provided

From Quest Diagnostics Nichols Institute San Juan Capistrano, SCV001470196.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

The variant results in a shift of the reading frame, and is therefore predicted to result in the loss of a functional protein. Found in at least one patient with expected phenotype for this gene, and not found in general population data.

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

From Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen, SCV001905529.2

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

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

From GeneDx, SCV002820717.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

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; Not observed at significant frequency in large population cohorts (gnomAD); Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; Also known as 1727delG; This variant is associated with the following publications: (PMID: 31825140, 19941162, 20104584, JiangY2021[preprint], 30702160, 34308104, 29053726, 11802209)

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

From CeGaT Center for Human Genetics Tuebingen, SCV002822064.18

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	6	not provided	not provided	clinical testing	not provided

Description

BRCA2: PVS1, PM2

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		6	not provided	not provided	not provided

Last Updated: May 25, 2025

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