NM_000059.4(BRCA2):c.8632+2T>C AND Hereditary breast ovarian cancer syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 19, 2023
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:: RCV001963311.6

Allele description [Variation Report for NM_000059.4(BRCA2):c.8632+2T>C]

NM_000059.4(BRCA2):c.8632+2T>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.8632+2T>C

HGVS:

NC_000013.11:g.32371102T>C
NG_012772.3:g.60623T>C
NM_000059.4:c.8632+2T>CMANE SELECT
NM_001406719.1:c.8536+2T>C
NM_001406720.1:c.8632+2T>C
NM_001406721.1:c.3700+2T>C
NM_001406722.1:c.2215+2T>C
LRG_293:g.60623T>C
NC_000013.10:g.32945239T>C
NM_000059.3:c.8632+2T>C

Links:

dbSNP: rs397507998

NCBI 1000 Genomes Browser:

rs397507998

Molecular consequence:

NM_000059.4:c.8632+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406719.1:c.8536+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406720.1:c.8632+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406721.1:c.3700+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406722.1:c.2215+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Name:: Hereditary breast ovarian cancer syndrome
Synonyms:: Hereditary breast and ovarian cancer syndrome; Hereditary breast and ovarian cancer; Hereditary breast and ovarian cancer syndrome (HBOC); See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0003582; MeSH: D061325; MedGen: C0677776; Orphanet: 145

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Mus musculus sulfatase modifying factor 2, mRNA (cDNA clone MGC:141062 IMAGE:400...
Mus musculus sulfatase modifying factor 2, mRNA (cDNA clone MGC:141062 IMAGE:40050522), complete cds
gi|115528397|gb|BC119480.2|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002241587	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 19, 2023)	germline	clinical testing	PubMed (8) [See all records that cite these PMIDs] 28975465, 30199306, 31131967, 24212087, 29774201, 30101128, 30623411, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002241587

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 19, 2023)

germline

clinical testing

PubMed (8)
[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

Expanding the spectrum of germline variants in cancer.

Siraj AK, Masoodi T, Bu R, Parvathareddy SK, Al-Badawi IA, Al-Sanea N, Ashari LH, Abduljabbar A, Alhomoud S, Al-Sobhi SS, Tulbah A, Ajarim D, Alzoman K, Aljuboury M, Yousef HB, Al-Dawish M, Al-Dayel F, Alkuraya FS, Al-Kuraya KS.

Hum Genet. 2017 Nov;136(11-12):1431-1444. doi: 10.1007/s00439-017-1845-0. Epub 2017 Oct 3.

PubMed [citation]

PMID:: 28975465

Prevalence of BRCA1 and BRCA2 Mutations Among High-Risk Saudi Patients With Breast Cancer.

Abulkhair O, Al Balwi M, Makram O, Alsubaie L, Faris M, Shehata H, Hashim A, Arun B, Saadeddin A, Ibrahim E.

J Glob Oncol. 2018 Aug;4:1-9. doi: 10.1200/JGO.18.00066.

PubMed [citation]

PMID:: 30199306
PMCID:: PMC6223490

See all PubMed Citations (8)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002241587.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (8)

Description

This sequence change affects a donor splice site in intron 20 of the BRCA2 gene. RNA analysis indicates that disruption of this splice site induces altered splicing and may result in an absent or disrupted protein product. This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individual(s) with breast and/or ovarian cancer (PMID: 28975465, 30199306). This variant is also known as c.8633+2T>C. ClinVar contains an entry for this variant (Variation ID: 1460449). Based on a multifactorial likelihood algorithm using genetic, in silico, and/or statistical data, this variant has been determined to have a high probability of being pathogenic (PMID: 31131967). Studies have shown that disruption of this splice site results in skipping of exon 20 and introduces a premature termination codon (PMID: 24212087, 29774201, 30101128, 30623411). The resulting mRNA is expected to undergo nonsense-mediated decay. For these reasons, this variant has been 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: Sep 29, 2024

ClinVar

Relating variation to medicine