NM_000059.4(BRCA2):c.67+1G>C AND Hereditary cancer-predisposing syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Mar 25, 2022
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:: RCV000217482.11

Allele description [Variation Report for NM_000059.4(BRCA2):c.67+1G>C]

NM_000059.4(BRCA2):c.67+1G>C

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.67+1G>C

HGVS:

NC_000013.11:g.32316528G>C
NG_012772.3:g.6049G>C
NG_017006.2:g.3836C>G
NM_000059.4:c.67+1G>CMANE SELECT
NM_001406719.1:c.67+1G>C
NM_001406720.1:c.67+1G>C
NM_001406721.1:c.67+1G>C
NM_001406722.1:c.-303+861G>C
LRG_293t1:c.67+1G>C
LRG_293:g.6049G>C
NC_000013.10:g.32890665G>C
NM_000059.3:c.67+1G>C

Links:

dbSNP: rs81002796

NCBI 1000 Genomes Browser:

rs81002796

Molecular consequence:

NM_001406722.1:c.-303+861G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_000059.4:c.67+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406719.1:c.67+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406720.1:c.67+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406721.1:c.67+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]

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

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000274286	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Mar 25, 2022)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 12938098, 17011978, 21063910, 22505045, 27257965 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000274286

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Mar 25, 2022)

germline

clinical testing

PubMed (5)
[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

Twenty-three novel BRCA1 and BRCA2 sequence alterations in breast and/or ovarian cancer families in Southern Germany.

Meyer P, Voigtlaender T, Bartram CR, Klaes R.

Hum Mutat. 2003 Sep;22(3):259.

PubMed [citation]

PMID:: 12938098

RNA-based analysis of BRCA1 and BRCA2 gene alterations.

Bonatti F, Pepe C, Tancredi M, Lombardi G, Aretini P, Sensi E, Falaschi E, Cipollini G, Bevilacqua G, Caligo MA.

Cancer Genet Cytogenet. 2006 Oct 15;170(2):93-101.

PubMed [citation]

PMID:: 17011978

See all PubMed Citations (5)

Details of each submission

From Ambry Genetics, SCV000274286.5

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

Description

The c.67+1G>C intronic pathogenic mutation results from a G to C substitution one nucleotide after coding exon 1 of the BRCA2 gene. This alteration has been detected in 1/507 unselected Chinese breast cancer patients (Zhong X et al. PLoS ONE 2016 Jun;11:e0156789). Additionally, two other disease-causing mutations at the same position, c.67+1G>A and c.67+1G>T, have been identified in families with HBOC (Meyer P et al. Hum. Mutat. 2003 Sep;22:259; Sagi M et al. Fam. Cancer. 2011 Mar;10(1):59-63) and functional studies have shown that both of these alterations result in skipping of exon 2 (Bonatti F et al. Cancer Genet Cytogenet. 2006 Oct 15;170(2):93-101; Houdayer C et al. Hum. Mutat. 2012 Aug;33:1228-38). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). In silico splice site analysis predicts that this alteration will weaken the native splice donor site. RNA studies have demonstrated that this alteration results in abnormal splicing in the set of samples tested (Ambry internal data). In addition to the clinical data presented in the literature, alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. As such, this alteration is classified 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: Nov 24, 2024

ClinVar

Relating variation to medicine