NM_000059.4(BRCA2):c.4111C>T (p.Gln1371Ter) AND Hereditary cancer-predisposing syndrome

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Apr 14, 2022
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:: RCV000131073.18

Allele description [Variation Report for NM_000059.4(BRCA2):c.4111C>T (p.Gln1371Ter)]

NM_000059.4(BRCA2):c.4111C>T (p.Gln1371Ter)

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.4111C>T (p.Gln1371Ter)

HGVS:

NC_000013.11:g.32338466C>T
NG_012772.3:g.27987C>T
NM_000059.4:c.4111C>TMANE SELECT
NP_000050.2:p.Gln1371Ter
NP_000050.3:p.Gln1371Ter
LRG_293t1:c.4111C>T
LRG_293:g.27987C>T
LRG_293p1:p.Gln1371Ter
NC_000013.10:g.32912603C>T
NM_000059.3:c.4111C>T
U43746.1:n.4339C>T
p.Gln1371*
p.Q1371*

Nucleotide change:

4339C>T

Protein change:

Q1371*

Links:

dbSNP: rs80358659

NCBI 1000 Genomes Browser:

rs80358659

Molecular consequence:

NM_000059.4:c.4111C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

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

Recent activity

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SAMN11533743 (1)
SRA
BBSome complex member BBS4 isoform 3 [Mus musculus]
BBSome complex member BBS4 isoform 3 [Mus musculus]
gi|2294372239|ref|NP_001398720.1|

Protein
References - Treatment of Degenerative Lumbar Spinal Stenosis
References - Treatment of Degenerative Lumbar Spinal Stenosis
Summary - Treatment of Attention-Deficit/Hyperactivity Disorder
Summary - Treatment of Attention-Deficit/Hyperactivity Disorder
LOC127405736 [Homo sapiens]
LOC127405736 [Homo sapiens]
Gene ID:127405736

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000186003	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Apr 14, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link,
SCV000688849	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Dec 14, 2021)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 22711857, 25371446, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000186003

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Apr 14, 2022)

germline

clinical testing

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

Citation Link,

SCV000688849

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Dec 14, 2021)

germline

clinical testing

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

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

BRCA mutation frequency and patterns of treatment response in BRCA mutation-positive women with ovarian cancer: a report from the Australian Ovarian Cancer Study Group.

Alsop K, Fereday S, Meldrum C, deFazio A, Emmanuel C, George J, Dobrovic A, Birrer MJ, Webb PM, Stewart C, Friedlander M, Fox S, Bowtell D, Mitchell G.

J Clin Oncol. 2012 Jul 20;30(21):2654-63. doi: 10.1200/JCO.2011.39.8545. Epub 2012 Jun 18. Erratum in: J Clin Oncol. 2012 Nov 20;30(33):4180.

PubMed [citation]

PMID:: 22711857
PMCID:: PMC3413277

Recurrent BRCA1 and BRCA2 mutations in Mexican women with breast cancer.

Torres-Mejía G, Royer R, Llacuachaqui M, Akbari MR, Giuliano AR, Martínez-Matsushita L, Angeles-Llerenas A, Ortega-Olvera C, Ziv E, Lazcano-Ponce E, Phelan CM, Narod SA.

Cancer Epidemiol Biomarkers Prev. 2015 Mar;24(3):498-505. doi: 10.1158/1055-9965.EPI-13-0980. Epub 2014 Nov 4.

PubMed [citation]

PMID:: 25371446
PMCID:: PMC4495576

See all PubMed Citations (3)

Details of each submission

From Ambry Genetics, SCV000186003.8

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

Description

The p.Q1371* pathogenic mutation (also known as c.4111C>T), located in coding exon 10 of the BRCA2 gene, results from a C to T substitution at nucleotide position 4111. This changes the amino acid from a glutamine to a stop codon within coding exon 10. This alteration was detected in three individuals from a cohort of 810 unselected, Hispanic women with a personal history of breast cancer (Torres-Mejía G et al. Cancer Epidemiol. Biomarkers Prev. 2015 Mar;24:498-505). 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

From Color Diagnostics, LLC DBA Color Health, SCV000688849.3

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

Description

This variant changes 1 nucleotide in exon 11 of the BRCA2 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. To our knowledge, functional studies have not been reported for this variant. This variant has been reported in individuals affected with breast cancer (PMID: 25371446) and ovarian cancer (PMID: 22711857). This variant has not been identified 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.

#	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: Nov 3, 2024

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