ClinVar Genomic variation as it relates to human health
NM_002878.4(RAD51D):c.547C>T (p.Gln183Ter)
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_002878.4(RAD51D):c.547C>T (p.Gln183Ter)
Variation ID: 142754 Accession: VCV000142754.22
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 17q12 17: 35106415 (GRCh38) [ NCBI UCSC ] 17: 33433434 (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 Feb 19, 2018 Sep 16, 2024 Feb 16, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_002878.4:c.547C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_002869.3:p.Gln183Ter nonsense NM_001142571.2:c.607C>T NP_001136043.1:p.Gln203Ter nonsense NM_133629.3:c.211C>T NP_598332.1:p.Gln71Ter nonsense NR_037711.2:n.573C>T non-coding transcript variant NR_037712.2:n.438C>T non-coding transcript variant NR_037714.1:n.299C>T non-coding transcript variant NC_000017.11:g.35106415G>A NC_000017.10:g.33433434G>A NG_031858.1:g.18455C>T LRG_516:g.18455C>T LRG_516t1:c.547C>T LRG_516p1:p.Gln183Ter - Protein change
- Q183*, Q71*, Q203*
- Other names
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- Canonical SPDI
- NC_000017.11:35106414:G:A
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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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- Links
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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RAD51D | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
34 | 1821 | |
RAD51L3-RFFL | - | - | - | GRCh38 | - | 1800 |
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/Likely pathogenic (3) |
criteria provided, multiple submitters, no conflicts
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Nov 22, 2021 | RCV000132135.11 | |
Pathogenic (3) |
criteria provided, multiple submitters, no conflicts
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Jan 4, 2024 | RCV000464954.11 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Feb 16, 2024 | RCV001566788.8 |
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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Pathogenic
(Aug 18, 2023)
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criteria provided, single submitter
Method: clinical testing
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Breast-ovarian cancer, familial, susceptibility to, 4
Affected status: unknown
Allele origin:
unknown
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Baylor Genetics
Accession: SCV004200382.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
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Likely pathogenic
(Aug 18, 2021)
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criteria provided, single submitter
Method: curation
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Sema4, Sema4
Accession: SCV002534826.1
First in ClinVar: Jun 24, 2022 Last updated: Jun 24, 2022
Comment:
To the best of our knowledge, the RAD51D c.547C>T (p.Q183X) variant has not been reported in individuals with RAD51D-related disease. This nonsense variant creates a … (more)
To the best of our knowledge, the RAD51D c.547C>T (p.Q183X) variant has not been reported in individuals with RAD51D-related disease. This nonsense variant creates a premature stop codon at residue 183 of the RAD51D protein. At this location, this is predicted to cause nonsense-mediated decay and result in an absent protein (loss of function). This variant is not reported in the population database Genome Aggregation Database (http://gnomad.broadinstitute.org, PMID: 32461654). This variant has been reported in ClinVar (Variation ID: 142754). Based on the current evidence available, this variant is interpreted as likely pathogenic. (less)
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Pathogenic
(Dec 16, 2023)
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criteria provided, single submitter
Method: clinical testing
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Breast-ovarian cancer, familial, susceptibility to, 4
Affected status: unknown
Allele origin:
germline
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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000551332.8
First in ClinVar: Apr 17, 2017 Last updated: Feb 14, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Gln183*) in the RAD51D gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Gln183*) in the RAD51D gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in RAD51D are known to be pathogenic (PMID: 21822267). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with RAD51D-related conditions. ClinVar contains an entry for this variant (Variation ID: 142754). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Nov 22, 2021)
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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: SCV000187206.8
First in ClinVar: Aug 06, 2014 Last updated: May 01, 2024 |
Comment:
The p.Q183* pathogenic mutation (also known as c.547C>T), located in coding exon 6 of the RAD51D gene, results from a C to T substitution at … (more)
The p.Q183* pathogenic mutation (also known as c.547C>T), located in coding exon 6 of the RAD51D gene, results from a C to T substitution at nucleotide position 547. This changes the amino acid from a glutamine to a stop codon within coding exon 6. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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)
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Pathogenic
(Apr 08, 2021)
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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: SCV000691344.2
First in ClinVar: Feb 19, 2018 Last updated: Mar 25, 2020 |
Comment:
This variant changes 1 nucleotide in exon 6 of the RAD51D gene, creating a premature translation stop signal. This variant is expected to result in … (more)
This variant changes 1 nucleotide in exon 6 of the RAD51D gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. To our knowledge, this variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of RAD51D 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
(May 10, 2023)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
unknown
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Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV004220179.1
First in ClinVar: Jan 06, 2024 Last updated: Jan 06, 2024 |
Comment:
This nonsense variant causes the premature termination of RAD51D protein synthesis. It also has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). In the … (more)
This nonsense variant causes the premature termination of RAD51D protein synthesis. It also has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). In the published literature, the variant has been reported in individuals with ovarian cancer (PMID: 28888541 (2017), 32107557 (2020)). Based on the available information, this variant is classified as pathogenic. (less)
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Pathogenic
(Jan 04, 2024)
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criteria provided, single submitter
Method: clinical testing
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Breast-ovarian cancer, familial, susceptibility to, 4
Affected status: unknown
Allele origin:
unknown
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Myriad Genetics, Inc.
Accession: SCV004932988.1
First in ClinVar: May 01, 2024 Last updated: May 01, 2024 |
Comment:
This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation.
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Pathogenic
(Feb 16, 2024)
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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: SCV001790360.5
First in ClinVar: Aug 19, 2021 Last updated: Sep 16, 2024 |
Comment:
Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of … (more)
Nonsense 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 significant frequency in large population cohorts (gnomAD); Observed in individuals with a personal and/or family history of breast and/or ovarian cancer (PMID: 28888541, 32107557); This variant is associated with the following publications: (PMID: 28152038, 32107557, 21822267, 28888541, 32359370) (less)
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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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BRIP1, RAD51C, and RAD51D mutations are associated with high susceptibility to ovarian cancer: mutation prevalence and precise risk estimates based on a pooled analysis of ~30,000 cases. | Suszynska M | Journal of ovarian research | 2020 | PMID: 32359370 |
Ovarian and Breast Cancer Risks Associated With Pathogenic Variants in RAD51C and RAD51D. | Yang X | Journal of the National Cancer Institute | 2020 | PMID: 32107557 |
Frequency of mutations in a large series of clinically ascertained ovarian cancer cases tested on multi-gene panels compared to reference controls. | Lilyquist J | Gynecologic oncology | 2017 | PMID: 28888541 |
Exome sequencing covers >98% of mutations identified on targeted next generation sequencing panels. | LaDuca H | PloS one | 2017 | PMID: 28152038 |
Germline mutations in RAD51D confer susceptibility to ovarian cancer. | Loveday C | Nature genetics | 2011 | PMID: 21822267 |
Text-mined citations for rs587782695 ...
HelpRecord last updated Sep 29, 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.