ClinVar Genomic variation as it relates to human health
NM_058216.3(RAD51C):c.732del (p.Ile244fs)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_058216.3(RAD51C):c.732del (p.Ile244fs)
Variation ID: 409860 Accession: VCV000409860.20
- Type and length
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Deletion, 1 bp
- Location
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Cytogenetic: 17q22 17: 58709884 (GRCh38) [ NCBI UCSC ] 17: 56787245 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Apr 17, 2017 Feb 28, 2024 Sep 10, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_058216.3:c.732del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_478123.1:p.Ile244fs frameshift NM_058216.2:c.732del NR_103872.2:n.607del non-coding transcript variant NC_000017.11:g.58709885del NC_000017.10:g.56787246del NG_023199.1:g.22284del LRG_314:g.22284del LRG_314t1:c.732del - Protein change
- I244fs
- Other names
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- Canonical SPDI
- NC_000017.11:58709883:TT:T
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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Allele frequency
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The frequency of the allele represented by this VCV record.
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Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
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The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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RAD51C | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
1780 | 1981 |
Conditions - Germline
Condition
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
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The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Pathogenic (1) |
criteria provided, single submitter
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Sep 10, 2023 | RCV000471345.10 | |
Likely pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Feb 10, 2023 | RCV000486595.2 | |
Pathogenic (1) |
criteria provided, single submitter
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Mar 15, 2017 | RCV000576324.4 | |
Likely pathogenic (1) |
criteria provided, single submitter
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Dec 16, 2016 | RCV000589098.3 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Jun 20, 2022 | RCV000775758.8 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Apr 5, 2023 | RCV003316570.4 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
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The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
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The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
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This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Likely pathogenic
(Dec 16, 2016)
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criteria provided, single submitter
Method: clinical testing
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Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000699821.1
First in ClinVar: Mar 17, 2018 Last updated: Mar 17, 2018 |
Comment:
Variant summary: The RAD51C c.732delT (p.Ile244Metfs) variant results in a premature termination codon, predicted to cause a truncated or absent RAD51C protein due to nonsense … (more)
Variant summary: The RAD51C c.732delT (p.Ile244Metfs) variant results in a premature termination codon, predicted to cause a truncated or absent RAD51C protein due to nonsense mediated decay, which are commonly known mechanisms for disease. One in silico tool predicts a damaging outcome for this variant. This variant was found in 1/130846 control chromosomes at a frequency of 0.0000076, which does not exceed the estimated maximal expected allele frequency of a pathogenic RAD51C variant (0.0000625). The variant was reported in two affected individuals and one control individual from the literature (Song_2015, Norquist_2016). While this variant is predicted to be pathogenic, more clinical or functional data is needed to definitively classify this variant as pathogenic. Taken together, this variant is classified as likely pathogenic. (less)
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Likely pathogenic
(Apr 08, 2016)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000569471.4
First in ClinVar: Apr 27, 2017 Last updated: Apr 27, 2017 |
Comment:
This deletion of one nucleotide in RAD51C is denoted c.732delT at the cDNA level and p.Ile244MetfsX9 (I244MfsX9) at the protein level. The normal sequence, with … (more)
This deletion of one nucleotide in RAD51C is denoted c.732delT at the cDNA level and p.Ile244MetfsX9 (I244MfsX9) at the protein level. The normal sequence, with the base that is deleted in braces, is GTAT[T]GCTT. The deletion causes a frameshift which changes an Isoleucine to a Methionine at codon 244, and creates a premature stop codon at position 9 of the new reading frame. This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. RAD51C c.732delT, also known as 731delT using alternate nomenclature, has been observed in at least two individuals with a personal and family history of ovarian and/or breast cancer (Song 2015). Based on the currently available information, we consider this deletion to be a likely pathogenic variant. (less)
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Pathogenic
(Jan 15, 2020)
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criteria provided, single submitter
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Color Diagnostics, LLC DBA Color Health
Accession: SCV000910195.3
First in ClinVar: May 20, 2019 Last updated: Jan 12, 2022 |
Comment:
This variant deletes 1 nucleotide in exon 5 of the RAD51C gene, creating a frameshift and premature translation stop signal. This variant is expected to … (more)
This variant deletes 1 nucleotide in exon 5 of the RAD51C gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of RAD51C function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic. (less)
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Pathogenic
(Mar 15, 2017)
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criteria provided, single submitter
Method: clinical testing
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Fanconi anemia complementation group O
Breast-ovarian cancer, familial, susceptibility to, 3
Affected status: unknown
Allele origin:
unknown
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Counsyl
Accession: SCV000677833.2
First in ClinVar: Jan 07, 2018 Last updated: Dec 24, 2022 |
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Pathogenic
(Sep 10, 2023)
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criteria provided, single submitter
Method: clinical testing
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Fanconi anemia complementation group O
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000550222.7
First in ClinVar: Apr 17, 2017 Last updated: Feb 28, 2024 |
Comment:
This premature translational stop signal has been observed in individual(s) with ovarian cancer (PMID: 26261251, 26720728). This variant is not present in population databases (gnomAD … (more)
This premature translational stop signal has been observed in individual(s) with ovarian cancer (PMID: 26261251, 26720728). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ile244Metfs*9) in the RAD51C gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in RAD51C are known to be pathogenic (PMID: 20400964, 21990120, 24800917, 29278735). This variant is also known as c.731delT. For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 409860). (less)
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Pathogenic
(Jun 20, 2022)
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criteria provided, single submitter
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV001188627.3
First in ClinVar: Mar 16, 2020 Last updated: Nov 29, 2022 |
Comment:
The c.732delT pathogenic mutation, located in coding exon 5 of the RAD51C gene, results from a deletion of one nucleotide at nucleotide position 732, causing … (more)
The c.732delT pathogenic mutation, located in coding exon 5 of the RAD51C gene, results from a deletion of one nucleotide at nucleotide position 732, causing a translational frameshift with a predicted alternate stop codon (p.I244Mfs*9). This alteration has been reported in a cohort of women with invasive epithelial ovarian cancer (Song H et al. J. Clin. Oncol., 2015 Sep;33:2901-7). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. (less)
Number of individuals with the variant: 1
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Pathogenic
(Apr 05, 2023)
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criteria provided, single submitter
Method: clinical testing
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Breast-ovarian cancer, familial, susceptibility to, 3
Affected status: unknown
Allele origin:
unknown
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Myriad Genetics, Inc.
Accession: SCV004019969.1
First in ClinVar: Jul 29, 2023 Last updated: Jul 29, 2023 |
Comment:
This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.
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Likely pathogenic
(Feb 10, 2023)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: not provided
Allele origin:
germline
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Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden
Accession: SCV004026262.1
First in ClinVar: Aug 19, 2023 Last updated: Aug 19, 2023 |
Comment:
PM4, PS4, PM2_SUP
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Pathogenic
(Jul 06, 2022)
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criteria provided, single submitter
Method: clinical testing
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Breast-ovarian cancer, familial, susceptibility to, 3
Affected status: unknown
Allele origin:
unknown
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Baylor Genetics
Accession: SCV004208034.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
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Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Expanding the FANCO/RAD51C associated phenotype: Cleft lip and palate and lobar holoprosencephaly, two rare findings in Fanconi anemia. | Jacquinet A | European journal of medical genetics | 2018 | PMID: 29278735 |
Inherited Mutations in Women With Ovarian Carcinoma. | Norquist BM | JAMA oncology | 2016 | PMID: 26720728 |
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 |
Deleterious RAD51C germline mutations rarely predispose to breast and ovarian cancer in Pakistan. | Rashid MU | Breast cancer research and treatment | 2014 | PMID: 24800917 |
Analysis of RAD51C germline mutations in high-risk breast and ovarian cancer families and ovarian cancer patients. | Thompson ER | Human mutation | 2012 | PMID: 21990120 |
Germline mutations in breast and ovarian cancer pedigrees establish RAD51C as a human cancer susceptibility gene. | Meindl A | Nature genetics | 2010 | PMID: 20400964 |
Text-mined citations for rs1060502601 ...
HelpRecord last updated Mar 05, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.