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NM_007294.4(BRCA1):c.5152T>G (p.Trp1718Gly)

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Interpretation:
Conflicting interpretations of pathogenicity​

Likely pathogenic(1);Uncertain significance(3)

Review status:
criteria provided, conflicting interpretations
Submissions:
5 (Most recent: May 19, 2021)
Last evaluated:
Apr 18, 2021
Accession:
VCV000627968.8
Variation ID:
627968
Description:
single nucleotide variant
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NM_007294.4(BRCA1):c.5152T>G (p.Trp1718Gly)

Allele ID
618559
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
17q21.31
Genomic location
17: 43063874 (GRCh38) GRCh38 UCSC
17: 41215891 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
LRG_292:g.154110T>G
LRG_292t1:c.5152T>G LRG_292p1:p.Trp1718Gly
NC_000017.10:g.41215891A>C
... more HGVS
Protein change
W1718G, W1671G, W1739G, W614G
Other names
-
Canonical SPDI
NC_000017.11:43063873:A:C
Functional consequence
functionally_abnormal [Sequence Ontology SO:0002218]
The saturation genome editing (SGE) assay for BRCA1 NM_007294.3:c.5152T>G, a MISSENSE variant, produced a function score of -1.87, corresponding to a functional classification of LOSS_OF_FUNCTION. SGE function score ranges for classification are as follows: ‘functional’, score > -0.748; ‘intermediate’, -0.748 > score > -1.328; ‘non-functional’, score < -1.328. The median synonymous SNV scored 0.0 and the median nonsense SNV scored -2.12. [submitted by Brotman Baty Institute,University of Washington]
Global minor allele frequency (GMAF)
-

Allele frequency
-
Links
dbSNP: rs1567769155
VarSome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Uncertain significance 2 criteria provided, multiple submitters, no conflicts Mar 14, 2019 RCV000772239.3
Conflicting interpretations of pathogenicity 2 criteria provided, conflicting interpretations Apr 18, 2021 RCV001050456.3
not provided 1 no assertion provided - RCV001076083.1
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
BRCA1 Sufficient evidence for dosage pathogenicity No evidence available GRCh38
GRCh37
12040 12208

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Uncertain significance
(Mar 14, 2019)
criteria provided, single submitter
Method: clinical testing
Hereditary cancer-predisposing syndrome
Allele origin: germline
Color Health, Inc
Accession: SCV000905357.2
Submitted: (May 19, 2020)
Evidence details
Uncertain significance
(Dec 22, 2017)
criteria provided, single submitter
Method: clinical testing
Hereditary cancer-predisposing syndrome
Allele origin: germline
Ambry Genetics
Accession: SCV001185534.2
Submitted: (Nov 30, 2020)
Evidence details
Comment:
The c.5152T>G variant (also known as p.W1718G), located in coding exon 16 of the BRCA1 gene, results from a T to G substitution at nucleotide … (more)
Uncertain significance
(Feb 25, 2019)
criteria provided, single submitter
Method: clinical testing
Hereditary breast and ovarian cancer syndrome
Allele origin: germline
Invitae
Accession: SCV001214564.2
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (1)
Comment:
This sequence change replaces tryptophan with glycine at codon 1718 of the BRCA1 protein (p.Trp1718Gly). The tryptophan residue is highly conserved and there is a … (more)
Likely pathogenic
(Apr 18, 2021)
criteria provided, single submitter
Method: clinical testing
Hereditary breast and ovarian cancer syndrome
Allele origin: germline
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV001623344.1
Submitted: (May 19, 2021)
Evidence details
Publications
PubMed (3)
Comment:
Variant summary: BRCA1 c.5152T>G (p.Trp1718Gly) results in a non-conservative amino acid change located in the BRCT domain (IPR001357) of the encoded protein sequence. Three of … (more)
not provided
(-)
no assertion provided
Method: in vitro
Breast-ovarian cancer, familial 1
Allele origin: not applicable
Brotman Baty Institute,University of Washington
Accession: SCV001241768.1
Submitted: (Nov 12, 2018)
Evidence details
Publications
PubMed (1)

Functional evidence

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Functional consequence Method Result Submitter Supporting information
functionally_abnormal
  1. saturation genome editing in haploid cells
  2. Method citation(s):
  1. LOSS_OF_FUNCTION:-1.8749475988444
Brotman Baty Institute,University of Washington
Accession: SCV001241768.1
Submitted: (Nov 12, 2018)
Evidence details
Publications
PubMed (1)
Comment:
The saturation genome editing (SGE) assay for BRCA1 NM_007294.3:c.5152T>G, a MISSENSE variant, produced a function score of -1.87, corresponding to a functional classification of LOSS_OF_FUNCTION. … (more)

Citations for this variant

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Title Author Journal Year Link
Breast Cancer Risk Genes - Association Analysis in More than 113,000 Women. Breast Cancer Association Consortium. The New England journal of medicine 2021 PMID: 33471991
Classification of VUS and unclassified variants in <i>BRCA1</i> BRCT repeats by molecular dynamics simulation. Sinha S Computational and structural biotechnology journal 2020 PMID: 32257056
Accurate classification of BRCA1 variants with saturation genome editing. Findlay GM Nature 2018 PMID: 30209399
https://sge.gs.washington.edu/BRCA1/ - - - -

Text-mined citations for rs1567769155...

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These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Dec 04, 2021