NM_007294.4(BRCA1):c.134+5G>A AND Hereditary breast and ovarian cancer syndrome

Clinical significance:Likely pathogenic (Last evaluated: Jul 5, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001221249.2

Allele description [Variation Report for NM_007294.4(BRCA1):c.134+5G>A]

NM_007294.4(BRCA1):c.134+5G>A

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.134+5G>A
HGVS:
  • NC_000017.11:g.43115721C>T
  • NG_005905.2:g.102263G>A
  • NM_007294.4:c.134+5G>AMANE SELECT
  • NM_007297.4:c.-8+8296G>A
  • NM_007298.3:c.134+5G>A
  • NM_007299.4:c.134+5G>A
  • NM_007300.4:c.134+5G>A
  • LRG_292t1:c.134+5G>A
  • LRG_292:g.102263G>A
  • NC_000017.10:g.41267738C>T
  • NM_007294.3:c.134+5G>A
  • U14680.1:n.253+5G>A
Nucleotide change:
IVS3+5G>A
Links:
Breast Cancer Information Core (BIC) (BRCA1): 253+5&base_change=G to A; dbSNP: rs80358038
NCBI 1000 Genomes Browser:
rs80358038
Molecular consequence:
  • NM_007294.4:c.134+5G>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_007297.4:c.-8+8296G>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_007298.3:c.134+5G>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_007299.4:c.134+5G>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_007300.4:c.134+5G>A - intron variant - [Sequence Ontology: SO:0001627]
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
SCV001393280Invitaecriteria provided, single submitter
Likely pathogenic
(Jul 5, 2019)
germlineclinical testing

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

Summary from all submissions

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

Citations

PubMed

The breast cancer information core: database design, structure, and scope.

Szabo C, Masiello A, Ryan JF, Brody LC.

Hum Mutat. 2000;16(2):123-31.

PubMed [citation]
PMID:
10923033

Aberrant 5' splice sites in human disease genes: mutation pattern, nucleotide structure and comparison of computational tools that predict their utilization.

Buratti E, Chivers M, Královicová J, Romano M, Baralle M, Krainer AR, Vorechovsky I.

Nucleic Acids Res. 2007;35(13):4250-63. Epub 2007 Jun 18.

PubMed [citation]
PMID:
17576681
PMCID:
PMC1934990
See all PubMed Citations (6)

Details of each submission

From Invitae, SCV001393280.2

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

Description

This sequence change falls in intron 3 of the BRCA1 gene. It does not directly change the encoded amino acid sequence of the BRCA1 protein, but it affects a nucleotide within the consensus splice site of the intron. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals in the Breast Cancer Information Core database (PMID: 10923033). ClinVar contains an entry for this variant (Variation ID: 91548). Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Experimental studies have shown that this variant disrupts mRNA splicing (PMID: 30209399). This variant disrupts the c.134+5G nucleotide in the BRCA1 gene. Other variant(s) that disrupt this nucleotide have been determined to be pathogenic (PMID: 29280214, 30209399). This suggests that this nucleotide is clinically-significant, and that variants that disrupt this position are likely to be disease-causing. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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

Last Updated: May 10, 2021

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