NM_007294.4(BRCA1):c.5153-1G>C AND Hereditary breast and ovarian cancer syndrome

Clinical significance:Pathogenic (Last evaluated: Nov 14, 2018)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000048827.5

Allele description [Variation Report for NM_007294.4(BRCA1):c.5153-1G>C]

NM_007294.4(BRCA1):c.5153-1G>C

Gene:
BRCA1:BRCA1 DNA repair associated [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
17q21.31
Genomic location:
Preferred name:
NM_007294.4(BRCA1):c.5153-1G>C
HGVS:
  • NC_000017.11:g.43063374C>G
  • NG_005905.2:g.154610G>C
  • NM_007294.4:c.5153-1G>CMANE SELECT
  • NM_007297.4:c.5012-1G>C
  • NM_007298.3:c.1841-1G>C
  • NM_007299.4:c.1841-1G>C
  • NM_007300.4:c.5216-1G>C
  • LRG_292t1:c.5153-1G>C
  • LRG_292:g.154610G>C
  • NC_000017.10:g.41215391C>G
  • NM_007294.3:c.5153-1G>C
  • U14680.1:n.5272-1G>C
Nucleotide change:
IVS18-1G>C
Links:
BRCA1-HCI: BRCA1_00144; Breast Cancer Information Core (BIC) (BRCA1): 5272-1&base_change=G to C; dbSNP: rs80358137
NCBI 1000 Genomes Browser:
rs80358137
Molecular consequence:
  • NM_007294.4:c.5153-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_007297.4:c.5012-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_007298.3:c.1841-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_007299.4:c.1841-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_007300.4:c.5216-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
Functional consequence:
functionally_abnormal [Sequence Ontology: SO:0002218] - Comment(s)

Condition(s)

Name:
Hereditary breast and ovarian cancer syndrome (HBOC)
Synonyms:
Hereditary breast and ovarian cancer; Hereditary breast and ovarian cancer syndrome (HBOC)
Identifiers:
MONDO: MONDO:0003582; MeSH: D061325; MedGen: C0677776; Orphanet: 145; OMIM: PS604370

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000076840Invitaecriteria provided, single submitter
Pathogenic
(Nov 14, 2018)
germlineclinical testing

PubMed (7)
[See all records that cite these PMIDs]

SCV000699211Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Pathogenic
(Aug 29, 2016)
germlineclinical testing

PubMed (6)
[See all records that cite these PMIDs]

LabCorp Variant Classification Summary - May 2015.docx

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Founder BRCA1/2 mutations in the Europe: implications for hereditary breast-ovarian cancer prevention and control.

Janavičius R.

EPMA J. 2010 Sep;1(3):397-412. doi: 10.1007/s13167-010-0037-y. Epub 2010 Jun 27.

PubMed [citation]
PMID:
23199084
PMCID:
PMC3405339

BRCA1 5272-1G>A and BRCA2 5374delTATG are founder mutations of high relevance for genetic counselling in breast/ovarian cancer families of Spanish origin.

Infante M, Durán M, Acedo A, Pérez-Cabornero L, Sanz DJ, García-González M, Beristain E, Esteban-Cardeñosa E, de la Hoya M, Teulé A, Vega A, Tejada MI, Lastra E, Miner C, Velasco EA.

Clin Genet. 2010 Jan;77(1):60-9. doi: 10.1111/j.1399-0004.2009.01272.x. Epub 2009 Nov 2.

PubMed [citation]
PMID:
19912264
See all PubMed Citations (10)

Details of each submission

From Invitae, SCV000076840.6

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (7)

Description

This sequence change affects an acceptor splice site in intron 17 of the BRCA1 gene. It is expected to disrupt mRNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (rs80358137, ExAC no frequency). This variant has been reported in the literature in many individuals and families affected with breast cancer (PMID: 8644702, 19912264, 25896959), and is reported as a putative founder mutation in the Spanish population (PMID: 23199084). Based on a multifactorial likelihood algorithm using genetic data, this variant has been determined to have a high probability of being pathogenic (PMID: 21990134, 17924331). This variant is also known as 5272-1G>C in the literature. ClinVar contains an entry for this variant (Variation ID: 37643). Experimental studies have shown that this splice site change results in altered splicing, which leads to an introduction of a premature termination codon (PMID: 20215541). For these reasons, this variant has been classified as Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000699211.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (6)

Description

Variant summary: The BRCA1 c.5153-1G>C variant involves the alteration of a conserved intronic nucleotide located in a known splice site with 5/5 splice prediction tools predict the loss of a splice site, although these predictions have yet to be functionally assessed. The variant of interest has not been observed in controls (ExAC, 1000 Gs, or ESP) and has been reported in multiple affected individuals. In addition, multiple reputable databases/clinical laboratories cite the variant as "pathogenic." Therefore, the variant of interest has been classified as Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Dec 4, 2021

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