NM_000059.4(BRCA2):c.2224C>T (p.Gln742Ter) AND not provided

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Apr 4, 2023
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:: RCV000212220.18

Allele description

NM_000059.4(BRCA2):c.2224C>T (p.Gln742Ter)

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

13q13.1

Genomic location:

Preferred name:

NM_000059.4(BRCA2):c.2224C>T (p.Gln742Ter)

Other names:

p.Q742*:CAA>TAA

HGVS:

NC_000013.11:g.32336579C>T
NG_012772.3:g.26100C>T
NM_000059.4:c.2224C>TMANE SELECT
NP_000050.2:p.Gln742Ter
NP_000050.3:p.Gln742Ter
LRG_293t1:c.2224C>T
LRG_293:g.26100C>T
LRG_293p1:p.Gln742Ter
NC_000013.10:g.32910716C>T
NM_000059.3:c.2224C>T
U43746.1:n.2452C>T
p.Gln742*

Nucleotide change:

2452C>T

Protein change:

Q742*

Links:

dbSNP: rs80358494

NCBI 1000 Genomes Browser:

rs80358494

Molecular consequence:

NM_000059.4:c.2224C>T - nonsense - [Sequence Ontology: SO:0001587]

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
SCV000210456	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Apr 4, 2023)	germline	clinical testing	Citation Link,
SCV000296604	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Pathogenic (Jul 20, 2021)	unknown	clinical testing	PubMed (10) [See all records that cite these PMIDs] 16030099, 25628955, 18284688, 28127413, 26681312, 26543556, 30630528, 29446198, 26467025, 26295337
SCV000805668	PreventionGenetics, part of Exact Sciences	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jul 10, 2017)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000210456

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Apr 4, 2023)

germline

clinical testing

Citation Link,

SCV000296604

Quest Diagnostics Nichols Institute San Juan Capistrano

criteria provided, single submitter

(Quest Diagnostics criteria)

Pathogenic
(Jul 20, 2021)

unknown

clinical testing

PubMed (10)
[See all records that cite these PMIDs]

SCV000805668

PreventionGenetics, part of Exact Sciences

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Jul 10, 2017)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

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

Citations

PubMed

Prevalence of BRCA mutations and founder effect in high-risk Hispanic families.

Weitzel JN, Lagos V, Blazer KR, Nelson R, Ricker C, Herzog J, McGuire C, Neuhausen S.

Cancer Epidemiol Biomarkers Prev. 2005 Jul;14(7):1666-71.

PubMed [citation]

PMID:: 16030099

Clinical and pathological characteristics of Hispanic BRCA-associated breast cancers in the American-Mexican border city of El Paso, TX.

Nahleh Z, Otoukesh S, Dwivedi AK, Mallawaarachchi I, Sanchez L, Saldivar JS, Cataneda K, Heydarian R.

Am J Cancer Res. 2015;5(1):466-71.

PubMed [citation]

PMID:: 25628955
PMCID:: PMC4300712

See all PubMed Citations (11)

Details of each submission

From GeneDx, SCV000210456.12

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

Description

Nonsense 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; Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; Not observed at significant frequency in large population cohorts (gnomAD); Also known as 2452C>T; This variant is associated with the following publications: (PMID: 28127413, 18284688, 30630528, 34413315, 25525159, 16030099, 26295337, 25716084, 25628955, 27221827, 29446198, 26543556, 29922827, 25371446, 33293522, 35875314, 31853058)

#	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 Quest Diagnostics Nichols Institute San Juan Capistrano, SCV000296604.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (10)

Description

This nonsense variant causes the premature termination of BRCA2 protein synthesis. The frequency of this variant in the general population, 0.000029 (1/34534 chromosomes, http://gnomad.broadinstitute.org), is consistent with pathogenicity. In the published literature, the variant has been reported in individuals with breast cancer in the published literature (PMID: 30630528 (2019), 29446198 (2018), 26681312 (2015), 26543556 (2015), 25628955 (2015), 16030099 (2005)). Based on the available information, this variant is classified as pathogenic.

#	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 PreventionGenetics, part of Exact Sciences, SCV000805668.1

#	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	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 8, 2024

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