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NM_007294.3(BRCA1):c.5470_5477delATTGGGCA (p.Ile1824Aspfs) AND Hereditary breast and ovarian cancer syndrome

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Dec 21, 2016
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:
RCV000049010.3

Allele description

NM_007294.3(BRCA1):c.5470_5477delATTGGGCA (p.Ile1824Aspfs)

Gene:
BRCA1:BRCA1, DNA repair associated [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
17q21.31
Genomic location:
Preferred name:
NM_007294.3(BRCA1):c.5470_5477delATTGGGCA (p.Ile1824Aspfs)
Other names:
5589del8
HGVS:
  • NC_000017.11:g.43045793_43045800delTGCCCAAT
  • NG_005905.2:g.172184_172191delATTGGGCA
  • NM_007294.3:c.5470_5477delATTGGGCA
  • NP_009225.1:p.Ile1824Aspfs
  • LRG_292t1:c.5470_5477delATTGGGCA
  • LRG_292:g.172184_172191delATTGGGCA
  • LRG_292p1:p.Ile1824Aspfs
  • NC_000017.10:g.41197810_41197817delTGCCCAAT
  • NM_007294.3:c.5470_5477del
  • NR_027676.1:n.5606_5613delATTGGGCA
  • U14680.1:n.5589_5596delATTGGGCA
  • p.I1824DFS*3
  • p.Ile1824Aspfs*3
Links:
Breast Cancer Information Core (BIC) (BRCA1): 5589&base_change=del ATTGGGCA; dbSNP: rs80357973
NCBI 1000 Genomes Browser:
rs80357973
Molecular consequence:
  • NM_007294.3:c.5470_5477delATTGGGCA - frameshift variant - [Sequence Ontology: SO:0001589]
  • NR_027676.1:n.5606_5613delATTGGGCA - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

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

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Assertion and evidence details

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Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000077023Invitae,
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Dec 21, 2016) 		germlineclinical testing

Citation Link

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Summary from all submissions

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

Details of each submission

From Invitae,, SCV000077023.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

This sequence change deletes 8 nucleotides from exon 23 of the BRCA1 mRNA (c.5470_5477delATTGGGCA), causing a frameshift at codon 1824. This creates a premature translational stop signal in the last exon of the BRCA1 mRNA (p.Ile1824Aspfs*3). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 40 amino acids of the BRCA1 protein. Loss-of-function variants in BRCA1 are known to be pathogenic. This particular variant has been reported in the literature in several individuals affected with breast and/or ovarian cancer (PMID: 25366075, 15117986, 25863477, 26824983, 16455195, 26848529, 26852015, 27257965). This variant is also known as 5589del8 in the literature. A different truncation downstream of this variant (p.Arg1835*) has been determined to be pathogenic (PMID: 8554067, 24504028, 16683254). This suggests that deletion of this region of the BRCA1 protein is causative of disease. For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: Dec 19, 2017