NM_000059.4(BRCA2):c.8754+1G>C AND Hereditary breast ovarian cancer syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 18, 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:: RCV001243882.5

Allele description [Variation Report for NM_000059.4(BRCA2):c.8754+1G>C]

NM_000059.4(BRCA2):c.8754+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.8754+1G>C

HGVS:

NC_000013.11:g.32376792G>C
NG_012772.3:g.66313G>C
NM_000059.4:c.8754+1G>CMANE SELECT
NM_001406719.1:c.8658+1G>C
NM_001406720.1:c.8754+1G>C
NM_001406721.1:c.3822+1G>C
NM_001406722.1:c.2337+1G>C
LRG_293t1:c.8754+1G>C
LRG_293:g.66313G>C
NC_000013.10:g.32950929G>C
NM_000059.3:c.8754+1G>C

Links:

dbSNP: rs397508006

NCBI 1000 Genomes Browser:

rs397508006

Molecular consequence:

NM_000059.4:c.8754+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406719.1:c.8658+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406720.1:c.8754+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406721.1:c.3822+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406722.1:c.2337+1G>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

Recent activity

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Rypticus saponaceus voucher USNM:FISH:401291 small subunit ribosomal RNA gene, p...
Rypticus saponaceus voucher USNM:FISH:401291 small subunit ribosomal RNA gene, partial sequence; internal transcribed spacer 1, 5.8S ribosomal RNA gene, and internal transcribed spacer 2, complete sequence; and large subunit ribosomal RNA gene, partial sequence
gi|2282139843|gb|OP151228.1|

Nucleotide
Mus musculus SEC24 homolog D, COPII coat complex component (Sec24d), mRNA
Mus musculus SEC24 homolog D, COPII coat complex component (Sec24d), mRNA
gi|46560564|ref|NM_027135.2|

Nucleotide
Fungal yeast sp. Urf2091 26S ribosomal RNA gene, partial sequence
Fungal yeast sp. Urf2091 26S ribosomal RNA gene, partial sequence
gi|148792985|gb|EF627499.1|

Nucleotide
Mus musculus timeless homolog (Drosophila), mRNA (cDNA clone IMAGE:30053561), pa...
Mus musculus timeless homolog (Drosophila), mRNA (cDNA clone IMAGE:30053561), partial cds
gi|31127195|gb|BC052884.1|

Nucleotide
PAU6 seripauperin PAU6 [Saccharomyces cerevisiae S288C]
PAU6 seripauperin PAU6 [Saccharomyces cerevisiae S288C]
Gene ID:855813

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001417069	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 18, 2022)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 18597679, 16199547, 20104584, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001417069

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 18, 2022)

germline

clinical testing

PubMed (4)
[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

Novel de novo BRCA2 mutation in a patient with a family history of breast cancer.

Hansen TV, Bisgaard ML, Jønson L, Albrechtsen A, Filtenborg-Barnkob B, Eiberg H, Ejlertsen B, Nielsen FC.

BMC Med Genet. 2008 Jul 2;9:58. doi: 10.1186/1471-2350-9-58.

PubMed [citation]

PMID:: 18597679
PMCID:: PMC2478678

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]

PMID:: 16199547
PMCID:: PMC1735933

See all PubMed Citations (4)

Details of each submission

From Invitae, SCV001417069.5

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

Description

ClinVar contains an entry for this variant (Variation ID: 922702). For these reasons, this variant has been classified as Pathogenic. Studies have shown that disruption of this splice site alters mRNA splicing and is expected to lead to the loss of protein expression (PMID: 18597679). This variant has not been reported in the literature in individuals affected with BRCA2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 21 of the BRCA2 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584).

#	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 1, 2024

ClinVar

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