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NM_058216.3(RAD51C):c.706-2A>G

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Interpretation:
Pathogenic/Likely pathogenic​

Review status:
criteria provided, multiple submitters, no conflicts
Submissions:
9 (Most recent: Mar 28, 2019)
Last evaluated:
Dec 11, 2018
Accession:
VCV000128209.4
Variation ID:
128209
Description:
single nucleotide variant
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NM_058216.3(RAD51C):c.706-2A>G

Allele ID
133666
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
17q22
Genomic location
17: 58709857 (GRCh38) GRCh38 UCSC
17: 56787218 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000017.10:g.56787218A>G
NC_000017.11:g.58709857A>G
NM_058216.3:c.706-2A>G splice acceptor
... more HGVS
Protein change
-
Other names
IVS4-2A>G
Functional consequence
effect on RNA splicing [Variation Ontology 0362]
Global minor allele frequency (GMAF)
-

Allele frequency
The Genome Aggregation Database (gnomAD), exomes 0.00002
Exome Aggregation Consortium (ExAC) 0.00002
The Genome Aggregation Database (gnomAD) 0.00003
Links
dbSNP: rs587780259
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Pathogenic 2 criteria provided, multiple submitters, no conflicts Dec 1, 2017 RCV000116178.8
Pathogenic 2 criteria provided, multiple submitters, no conflicts Oct 31, 2018 RCV000576612.2
Pathogenic 2 criteria provided, single submitter Dec 11, 2018 RCV000234445.6
Likely pathogenic 1 criteria provided, single submitter Apr 30, 2018 RCV000254687.2
Pathogenic 1 criteria provided, single submitter - RCV000456123.1
Likely pathogenic 1 no assertion criteria provided Dec 1, 2018 RCV000785234.1
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
RAD51C - - GRCh38
GRCh37
829 844

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Pathogenic
(Jan 12, 2017)
criteria provided, single submitter
Method: clinical testing
Fanconi anemia, complementation group O
Breast-ovarian cancer, familial 3
Allele origin: unknown
Counsyl
Accession: SCV000677780.1
Submitted: (Jun 22, 2017)
Evidence details
Publications
PubMed (2)
Pathogenic
(Feb 10, 2016)
criteria provided, single submitter
Method: clinical testing
Hereditary cancer-predisposing syndrome
Allele origin: germline
Color
Accession: SCV000686377.1
Submitted: (Oct 26, 2017)
Evidence details
Pathogenic
(Oct 31, 2018)
criteria provided, single submitter
Method: clinical testing
Fanconi anemia, complementation group O
Breast-ovarian cancer, familial 3
Allele origin: unknown
Fulgent Genetics,Fulgent Genetics
Accession: SCV000893462.1
Submitted: (Nov 14, 2018)
Evidence details
Publications
PubMed (1)
DOI: 10.1038/gim.2015.30
Likely pathogenic
(Apr 30, 2018)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV000150087.11
Submitted: (Jan 29, 2019)
Evidence details
Comment:
This variant is denoted RAD51C c.706-2A>G or IVS4-2A>G and consists of an A>G nucleotide substitution at the -2 position of intron 4 of the RAD51C ... (more)
Pathogenic
(-)
criteria provided, single submitter
Method: clinical testing
613399
(Autosomal dominant inheritance)
Allele origin: germline
Laboratoire de Biologie et Génétique du Cancer,Centre François Baclesse
Accession: SCV000536677.1
Submitted: (Mar 06, 2017)
Evidence details
Publications
PubMed (1)
Pathogenic
(Dec 01, 2017)
criteria provided, single submitter
Method: clinical testing
Hereditary cancer-predisposing syndrome
Allele origin: germline
Ambry Genetics
Accession: SCV000186640.5
Submitted: (Jul 30, 2018)
Evidence details
Publications
PubMed (6)
Comment:
Lines of evidence used in support of classification: Alterations at the canonical donor/acceptor sites (+/- 1, 2) without other strong (b-level) evidence supporting pathogenicity,Functionally-validated splicing ... (more)
Pathogenic
(Dec 11, 2018)
criteria provided, single submitter
Method: clinical testing
Fanconi anemia, complementation group O
Allele origin: germline
Invitae
Accession: SCV000291240.6
Submitted: (Mar 28, 2019)
Evidence details
Publications
PubMed (11)
Comment:
This sequence change affects an acceptor splice site in intron 4 of the RAD51C gene. It is expected to disrupt RNA splicing and likely results ... (more)
Pathogenic
(Aug 16, 2016)
no assertion criteria provided
Method: research
Fanconi anemia, complementation group O
Allele origin: maternal
Division of Human Genetics,Children's Hospital of Philadelphia
Study: CSER-PediSeq
Accession: SCV000536783.1
Submitted: (Jan 23, 2017)
Evidence details
Publications
PubMed (2)
Likely pathogenic
(Dec 01, 2018)
no assertion criteria provided
Method: research
Ovarian Neoplasms
Allele origin: germline
German Consortium for Hereditary Breast and Ovarian Cancer Center Cologne,University Hospital Cologne
Accession: SCV000923802.1
Submitted: (Feb 22, 2019)
Evidence details

Citations for this variant

Title Author Journal Year Link
Detecting splicing patterns in genes involved in hereditary breast and ovarian cancer. Davy G European journal of human genetics : EJHG 2017 PMID: 28905878
Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria. Nykamp K Genetics in medicine : official journal of the American College of Medical Genetics 2017 PMID: 28492532
Pathogenic and likely pathogenic variant prevalence among the first 10,000 patients referred for next-generation cancer panel testing. Susswein LR Genetics in medicine : official journal of the American College of Medical Genetics 2016 PMID: 26681312
Contribution of Germline Mutations in the RAD51B, RAD51C, and RAD51D Genes to Ovarian Cancer in the Population. Song H Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2015 PMID: 26261251
Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Richards S Genetics in medicine : official journal of the American College of Medical Genetics 2015 PMID: 25741868
Inherited mutations in 17 breast cancer susceptibility genes among a large triple-negative breast cancer cohort unselected for family history of breast cancer. Couch FJ Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2015 PMID: 25452441
Deleterious RAD51C germline mutations rarely predispose to breast and ovarian cancer in Pakistan. Rashid MU Breast cancer research and treatment 2014 PMID: 24800917
Next-generation sequencing for the diagnosis of hereditary breast and ovarian cancer using genomic capture targeting multiple candidate genes. Castéra L European journal of human genetics : EJHG 2014 PMID: 24549055
RAD51C--a new human cancer susceptibility gene for sporadic squamous cell carcinoma of the head and neck (HNSCC). Scheckenbach K Oral oncology 2014 PMID: 24315737
Germline mutation in the RAD51B gene confers predisposition to breast cancer. Golmard L BMC cancer 2013 PMID: 24139550
Germline RAD51C mutations confer susceptibility to ovarian cancer. Loveday C Nature genetics 2012 PMID: 22538716
Analysis of RAD51C germline mutations in high-risk breast and ovarian cancer families and ovarian cancer patients. Thompson ER Human mutation 2012 PMID: 21990120
Mutations in 12 genes for inherited ovarian, fallopian tube, and peritoneal carcinoma identified by massively parallel sequencing. Walsh T Proceedings of the National Academy of Sciences of the United States of America 2011 PMID: 22006311
Germline mutations in breast and ovarian cancer pedigrees establish RAD51C as a human cancer susceptibility gene. Meindl A Nature genetics 2010 PMID: 20400964

Record last updated Aug 25, 2019