This variant deletes 2 nucleotides in exon 2 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 been reported in males affected with breast cancer (PMID: 32365798) and metastatic prostate cancer (PMID: 27433846). This variant has been identified in 3/251400 chromosomes 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.
ClinVar Genomic variation as it relates to human health
NM_058216.3(RAD51C):c.181_182del (p.Leu61fs)
Germline
Classification
Help
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.
(9)
Help
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.
Pathogenic
9
criteria provided, multiple submitters, no conflicts
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_058216.3(RAD51C):c.181_182del (p.Leu61fs)
Variation ID: 187716 Accession: VCV000187716.27
- Type and length
-
Microsatellite, 2 bp
- Location
-
Cytogenetic: 17q22 17: 58694964-58694965 (GRCh38) [ NCBI UCSC ] 17: 56772325-56772326 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
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 Jul 9, 2018 Jun 17, 2024 Feb 29, 2024 - HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_058216.3:c.181_182del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_478123.1:p.Leu61fs frameshift NM_002876.4:c.181_182del NP_002867.1:p.Leu61fs frameshift NM_058216.2:c.181_182del NR_103872.2:n.221CT[1] non-coding transcript variant NR_103873.1:n.147CT[1] non-coding transcript variant NC_000017.11:g.58694964CT[1] NC_000017.10:g.56772325CT[1] NG_023199.1:g.7363CT[1] NG_047169.1:g.2113AG[1] LRG_314:g.7363CT[1] LRG_314t1:c.181_182del - Protein change
- L61fs
- Other names
-
NM_058216.1:c.181_182del
- Canonical SPDI
- NC_000017.11:58694963:CTCT:CT
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- -
-
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.
- -
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
- -
- Links
Genes
| Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
|---|---|---|---|---|---|---|
| HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
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. |
|||
| RAD51C | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
1858 | 2067 | |
Conditions - Germline
| Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
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
Help
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
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
|---|---|---|---|---|
| Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
|
Feb 7, 2023 | RCV000167466.10 | |
| Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
|
Jan 9, 2024 | RCV000456496.14 | |
| Pathogenic (2) |
criteria provided, single submitter
|
Jan 25, 2023 | RCV000657321.5 | |
| Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
|
Feb 29, 2024 | RCV003468811.3 | |
|
RAD51C-related disorder
|
Pathogenic (1) |
criteria provided, single submitter
|
Sep 1, 2022 | RCV004535139.1 |
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
Help
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
Help
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
Help
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. |
|
|---|---|---|---|---|---|
|
Pathogenic
(Dec 14, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Color Diagnostics, LLC DBA Color Health
Accession: SCV001340644.3
First in ClinVar: Mar 25, 2020 Last updated: Feb 14, 2024 |
Comment:
This variant deletes 2 nucleotides in exon 2 of the RAD51C gene, creating a frameshift and premature translation stop signal. This variant is expected to … (more)
This variant deletes 2 nucleotides in exon 2 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 been reported in males affected with breast cancer (PMID: 32365798) and metastatic prostate cancer (PMID: 27433846). This variant has been identified in 3/251400 chromosomes 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)
|
|
|
Pathogenic
(Feb 07, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV000218322.8
First in ClinVar: Mar 24, 2015 Last updated: May 01, 2024 |
Comment:
The c.181_182delCT pathogenic mutation, located in coding exon 2 of the RAD51C gene, results from a deletion of two nucleotides at nucleotide positions 181 to … (more)
The c.181_182delCT pathogenic mutation, located in coding exon 2 of the RAD51C gene, results from a deletion of two nucleotides at nucleotide positions 181 to 182, causing a translational frameshift with a predicted alternate stop codon (p.L61Afs*11). This alteration, designated as c.179_180del, was identified in 1/692 men with metastatic prostate cancer who were unselected for family history of cancer or age at diagnosis (Pritchard CC et al. N. Engl. J. Med., 2016 Aug;375:443-53). 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)
|
|
|
Pathogenic
(Feb 29, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 3
Affected status: unknown
Allele origin:
unknown
|
Baylor Genetics
Accession: SCV004207935.2
First in ClinVar: Dec 30, 2023 Last updated: Jun 17, 2024 |
|
|
|
Pathogenic
(Sep 01, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
RAD51C-related condition
Affected status: unknown
Allele origin:
germline
|
PreventionGenetics, part of Exact Sciences
Accession: SCV004113257.1
First in ClinVar: Nov 20, 2023 Last updated: Nov 20, 2023 |
Comment:
The RAD51C c.181_182delCT variant is predicted to result in a frameshift and premature protein termination (p.Leu61Alafs*11). This variant (reported as c.179_180del) was identified in an … (more)
The RAD51C c.181_182delCT variant is predicted to result in a frameshift and premature protein termination (p.Leu61Alafs*11). This variant (reported as c.179_180del) was identified in an individual affected with metastatic prostate cancer, and was classified as pathogenic (Table S1, Pritchard et al. 2016. PubMed ID: 27433846). This variant is reported in 0.0046% of alleles in individuals of European (Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/17-56772324-ACT-A) and has been interpreted as pathogenic in the ClinVar database (https://www.ncbi.nlm.nih.gov/clinvar/variation/187716/). Frameshift variants in RAD51C are expected to be pathogenic. This variant is interpreted as pathogenic. (less)
|
|
|
Pathogenic
(Apr 26, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Fanconi anemia complementation group O
Affected status: unknown
Allele origin:
germline
|
Revvity Omics, Revvity
Accession: SCV002019635.3
First in ClinVar: Nov 29, 2021 Last updated: Feb 04, 2024 |
|
|
|
Pathogenic
(Jan 02, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 3
Affected status: unknown
Allele origin:
unknown
|
Myriad Genetics, Inc.
Accession: SCV004930367.1
First in ClinVar: May 01, 2024 Last updated: May 01, 2024 |
Comment:
This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.
|
|
|
Pathogenic
(Jan 25, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000779052.4
First in ClinVar: Jul 09, 2018 Last updated: Nov 11, 2023 |
Comment:
Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not … (more)
Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at a significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 27433846, 27806231, 30947698, 32365798, 35220195, 29625052, 29922827, 32107557) (less)
|
|
|
Pathogenic
(Jan 09, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Fanconi anemia complementation group O
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000550223.10
First in ClinVar: Apr 17, 2017 Last updated: Feb 28, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Leu61Alafs*11) in the RAD51C gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Leu61Alafs*11) 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 present in population databases (rs754525165, gnomAD 0.004%). This premature translational stop signal has been observed in individual(s) with prostate cancer (PMID: 27433846). This variant is also known as c.179_180del. ClinVar contains an entry for this variant (Variation ID: 187716). For these reasons, this variant has been classified as Pathogenic. (less)
|
|
|
Pathogenic
(Dec 04, 2019)
|
no assertion criteria provided
Method: curation
|
not provided
Affected status: yes
Allele origin:
germline
|
Leiden Open Variation Database
Accession: SCV001365248.1
First in ClinVar: Jun 29, 2020 Last updated: Jun 29, 2020 |
Comment:
Curator: Arleen D. Auerbach. Submitter to LOVD: Andreas Laner.
|
Comment:
Comment:
The c.181_182delCT pathogenic mutation, located in coding exon 2 of the RAD51C gene, results from a deletion of two nucleotides at nucleotide positions 181 to 182, causing a translational frameshift with a predicted alternate stop codon (p.L61Afs*11). This alteration, designated as c.179_180del, was identified in 1/692 men with metastatic prostate cancer who were unselected for family history of cancer or age at diagnosis (Pritchard CC et al. N. Engl. J. Med., 2016 Aug;375:443-53). 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.
Comment:
The RAD51C c.181_182delCT variant is predicted to result in a frameshift and premature protein termination (p.Leu61Alafs*11). This variant (reported as c.179_180del) was identified in an individual affected with metastatic prostate cancer, and was classified as pathogenic (Table S1, Pritchard et al. 2016. PubMed ID: 27433846). This variant is reported in 0.0046% of alleles in individuals of European (Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/17-56772324-ACT-A) and has been interpreted as pathogenic in the ClinVar database (https://www.ncbi.nlm.nih.gov/clinvar/variation/187716/). Frameshift variants in RAD51C are expected to be pathogenic. This variant is interpreted as pathogenic.
Comment:
This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.
Comment:
Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at a significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 27433846, 27806231, 30947698, 32365798, 35220195, 29625052, 29922827, 32107557)
Comment:
This sequence change creates a premature translational stop signal (p.Leu61Alafs*11) 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 present in population databases (rs754525165, gnomAD 0.004%). This premature translational stop signal has been observed in individual(s) with prostate cancer (PMID: 27433846). This variant is also known as c.179_180del. ClinVar contains an entry for this variant (Variation ID: 187716). For these reasons, this variant has been classified as Pathogenic.
Comment:
Curator: Arleen D. Auerbach. Submitter to LOVD: Andreas Laner.
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. |
Comment:
This variant deletes 2 nucleotides in exon 2 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 been reported in males affected with breast cancer (PMID: 32365798) and metastatic prostate cancer (PMID: 27433846). This variant has been identified in 3/251400 chromosomes 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.
Comment:
The c.181_182delCT pathogenic mutation, located in coding exon 2 of the RAD51C gene, results from a deletion of two nucleotides at nucleotide positions 181 to 182, causing a translational frameshift with a predicted alternate stop codon (p.L61Afs*11). This alteration, designated as c.179_180del, was identified in 1/692 men with metastatic prostate cancer who were unselected for family history of cancer or age at diagnosis (Pritchard CC et al. N. Engl. J. Med., 2016 Aug;375:443-53). 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.
Comment:
The RAD51C c.181_182delCT variant is predicted to result in a frameshift and premature protein termination (p.Leu61Alafs*11). This variant (reported as c.179_180del) was identified in an individual affected with metastatic prostate cancer, and was classified as pathogenic (Table S1, Pritchard et al. 2016. PubMed ID: 27433846). This variant is reported in 0.0046% of alleles in individuals of European (Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/17-56772324-ACT-A) and has been interpreted as pathogenic in the ClinVar database (https://www.ncbi.nlm.nih.gov/clinvar/variation/187716/). Frameshift variants in RAD51C are expected to be pathogenic. This variant is interpreted as pathogenic.
Comment:
This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.
Comment:
Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at a significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 27433846, 27806231, 30947698, 32365798, 35220195, 29625052, 29922827, 32107557)
Comment:
This sequence change creates a premature translational stop signal (p.Leu61Alafs*11) 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 present in population databases (rs754525165, gnomAD 0.004%). This premature translational stop signal has been observed in individual(s) with prostate cancer (PMID: 27433846). This variant is also known as c.179_180del. ClinVar contains an entry for this variant (Variation ID: 187716). For these reasons, this variant has been classified as Pathogenic.
Comment:
Curator: Arleen D. Auerbach. Submitter to LOVD: Andreas Laner.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Male Breast Cancer: Results of the Application of Multigene Panel Testing to an Italian Cohort of Patients. | Tedaldi G | Diagnostics (Basel, Switzerland) | 2020 | PMID: 32365798 |
| 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 DNA-Repair Gene Mutations in Men with Metastatic Prostate Cancer. | Pritchard CC | The New England journal of medicine | 2016 | PMID: 27433846 |
| 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 rs786203945 ...
HelpThese 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 Nov 25, 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.