ClinVar Genomic variation as it relates to human health
NM_002878.4(RAD51D):c.451C>T (p.Gln151Ter)
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.451C>T (p.Gln151Ter)
Variation ID: 141452 Accession: VCV000141452.42
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 17q12 17: 35107017 (GRCh38) [ NCBI UCSC ] 17: 33434036 (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 Jan 6, 2017 Jun 17, 2024 Mar 25, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_002878.4:c.451C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_002869.3:p.Gln151Ter nonsense NM_001142571.2:c.511C>T NP_001136043.1:p.Gln171Ter nonsense NM_133629.3:c.145-536C>T intron variant NR_037711.2:n.477C>T non-coding transcript variant NC_000017.11:g.35107017G>A NC_000017.10:g.33434036G>A NG_031858.1:g.17853C>T LRG_516:g.17853C>T LRG_516t1:c.451C>T LRG_516p1:p.Gln151Ter - Protein change
- Q151*, Q171*
- Other names
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- Canonical SPDI
- NC_000017.11:35107016: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.
The Genome Aggregation Database (gnomAD), exomes 0.00000
Trans-Omics for Precision Medicine (TOPMed) 0.00001
The Genome Aggregation Database (gnomAD) 0.00002
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 |
26 | 1787 | |
RAD51L3-RFFL | - | - | - | GRCh38 | - | 1773 |
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 (2) |
criteria provided, multiple submitters, no conflicts
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May 16, 2022 | RCV000129970.12 | |
Pathogenic/Likely pathogenic (6) |
criteria provided, multiple submitters, no conflicts
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Mar 25, 2024 | RCV000409676.15 | |
Pathogenic (3) |
criteria provided, multiple submitters, no conflicts
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Jun 27, 2023 | RCV000485836.21 | |
Pathogenic (1) |
no assertion criteria provided
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Jun 11, 2019 | RCV001271048.2 | |
Pathogenic (1) |
criteria provided, single submitter
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Aug 9, 2022 | RCV002281953.2 |
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
(Nov 11, 2019)
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criteria provided, single submitter
Method: clinical testing
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Breast-ovarian cancer, familial, susceptibility to, 4
Affected status: yes
Allele origin:
germline
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Institute of Human Genetics, University of Leipzig Medical Center
Accession: SCV001428760.1
First in ClinVar: Aug 15, 2020 Last updated: Aug 15, 2020 |
Number of individuals with the variant: 1
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Pathogenic
(Mar 04, 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: SCV000691340.3
First in ClinVar: Feb 19, 2018 Last updated: Jan 12, 2022 |
Comment:
This variant changes 1 nucleotide in exon 5 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 5 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, functional studies have not been reported for this variant. This variant has been reported in an individual affected with ovarian cancer (PMID: 26720728). This variant has been identified in 1/251464 chromosomes 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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Likely pathogenic
(Nov 02, 2016)
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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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Counsyl
Accession: SCV000489612.2
First in ClinVar: Jan 06, 2017 Last updated: Dec 24, 2022 |
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Pathogenic
(Apr 06, 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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Myriad Genetics, Inc.
Accession: SCV004017752.1
First in ClinVar: Jul 29, 2023 Last updated: Jul 29, 2023 |
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
(Jun 27, 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: SCV004220176.1
First in ClinVar: Jan 06, 2024 Last updated: Jan 06, 2024 |
Comment:
The RAD51D c.451C>T (p.Gln151*) variant causes the premature termination of RAD51D protein synthesis. This variant has been reported in the published literature in individuals with … (more)
The RAD51D c.451C>T (p.Gln151*) variant causes the premature termination of RAD51D protein synthesis. This variant has been reported in the published literature in individuals with ovarian cancer (PMID: 26720728 (2016)), breast cancer (PMID: 28724667 (2017), 30111881 (2018), 30165555 (2018), 31300551 (2020)), and lung cancer (PMID: 35273153 (2022)). In a large breast cancer association study, this variant was reported in individuals with breast cancer as well as a healthy individual (PMID: 33471991 (2021), https://databases.lovd.nl/shared/variants/RAD51D). The frequency of this variant in the general population, 0.000004 (1/251464 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is consistent with pathogenicity. Based on the available information, this variant is classified as pathogenic. (less)
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Pathogenic
(May 16, 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: SCV000184794.8
First in ClinVar: Aug 06, 2014 Last updated: May 01, 2024 |
Comment:
The p.Q151* pathogenic mutation (also known as c.451C>T), located in coding exon 5 of the RAD51D gene, results from a C to T substitution at … (more)
The p.Q151* pathogenic mutation (also known as c.451C>T), located in coding exon 5 of the RAD51D gene, results from a C to T substitution at nucleotide position 451. This changes the amino acid from a glutamine to a stop codon within coding exon 5. This mutation has been reported in a Greek proband with breast cancer who also had a family history of breast and ovarian cancer (Konstanta I et al. J. Hum. Genet. 2018 Nov;63(11):1149-1158). 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
(Mar 25, 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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Baylor Genetics
Accession: SCV004200445.2
First in ClinVar: Dec 30, 2023 Last updated: Jun 17, 2024 |
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Pathogenic
(Oct 31, 2018)
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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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Fulgent Genetics, Fulgent Genetics
Accession: SCV000894111.1
First in ClinVar: Mar 31, 2019 Last updated: Mar 31, 2019 |
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Pathogenic
(Sep 26, 2017)
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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: SCV000565466.5
First in ClinVar: Apr 27, 2017 Last updated: Dec 19, 2017 |
Comment:
This pathogenic variant is denoted RAD51D c.451C>T at the cDNA level and p.Gln151Ter (Q151X) at the protein level. The substitution creates a nonsense variant, which … (more)
This pathogenic variant is denoted RAD51D c.451C>T at the cDNA level and p.Gln151Ter (Q151X) at the protein level. The substitution creates a nonsense variant, which changes a Glutamine to a premature stop codon (CAG>TAG), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant has been reported in individuals with breast or ovarian cancer and is considered pathogenic (Norquist 2015, Sun 2017). (less)
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Pathogenic
(Aug 09, 2022)
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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: SCV002571905.1
First in ClinVar: Sep 17, 2022 Last updated: Sep 17, 2022 |
Comment:
Variant summary: RAD51D c.451C>T (p.Gln151X), also referred to as c.511C>T (p.Gln171X), results in a premature termination codon, predicted to cause a truncation of the encoded … (more)
Variant summary: RAD51D c.451C>T (p.Gln151X), also referred to as c.511C>T (p.Gln171X), results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 4e-06 in 251464 control chromosomes (gnomAD). c.451C>T has been reported in the literature in multiple individuals a personal and/or family history of breast and/or ovarian cancer (e.g. Norquist_2016, Stafford_2017, Sun_2017, Konstanta_2018, Mittal_2022). These data indicate that the variant is very likely to be associated with Hereditary Breast And Ovarian Cancer Syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Nine submitters have provided clinical-significance assessments for this variant to ClinVar after 2014 and all classified the variant as pathogenic (n=8) or likely pathogenic (n=1). Based on the evidence outlined above, the variant was classified as pathogenic. (less)
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Pathogenic
(Jan 28, 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:
germline
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Invitae
Accession: SCV000651748.7
First in ClinVar: Dec 26, 2017 Last updated: Feb 20, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Gln151*) 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.Gln151*) 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 present in population databases (rs587781756, gnomAD 0.0009%). This premature translational stop signal has been observed in individual(s) with ovarian cancer (PMID: 26720728, 28591191). This variant is also known as c.511C>T and p.Q171*. ClinVar contains an entry for this variant (Variation ID: 141452). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Jan 01, 2021)
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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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CeGaT Center for Human Genetics Tuebingen
Accession: SCV001500123.19
First in ClinVar: Mar 14, 2021 Last updated: Jun 17, 2024 |
Number of individuals with the variant: 1
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Pathogenic
(Jun 11, 2019)
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no assertion criteria provided
Method: clinical testing
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Breast and/or ovarian cancer
Affected status: yes
Allele origin:
germline
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CZECANCA consortium
Accession: SCV001451867.1
First in ClinVar: Dec 24, 2020 Last updated: Dec 24, 2020 |
Number of individuals with the variant: 1
Ethnicity/Population group: Slavic
Geographic origin: Czech Republic
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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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Clinical and genomic features of Chinese lung cancer patients with germline mutations. | Peng W | Nature communications | 2022 | PMID: 35273153 |
Profile of Pathogenic Mutations and Evaluation of Germline Genetic Testing Criteria in Consecutive Breast Cancer Patients Treated at a North Indian Tertiary Care Center. | Mittal A | Annals of surgical oncology | 2022 | PMID: 34601666 |
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 |
Ovarian and Breast Cancer Risks Associated With Pathogenic Variants in RAD51C and RAD51D. | Yang X | Journal of the National Cancer Institute | 2020 | PMID: 32107557 |
One in three highly selected Greek patients with breast cancer carries a loss-of-function variant in a cancer susceptibility gene. | Fostira F | Journal of medical genetics | 2020 | PMID: 31300551 |
Associations between RAD51D germline mutations and breast cancer risk and survival in BRCA1/2-negative breast cancers. | Chen X | Annals of oncology : official journal of the European Society for Medical Oncology | 2018 | PMID: 30165555 |
Contribution of RAD51D germline mutations in breast and ovarian cancer in Greece. | Konstanta I | Journal of human genetics | 2018 | PMID: 30111881 |
Germline Mutations in Cancer Susceptibility Genes in a Large Series of Unselected Breast Cancer Patients. | Sun J | Clinical cancer research : an official journal of the American Association for Cancer Research | 2017 | PMID: 28724667 |
Reanalysis of BRCA1/2 negative high risk ovarian cancer patients reveals novel germline risk loci and insights into missing heritability. | Stafford JL | PloS one | 2017 | PMID: 28591191 |
Inherited Mutations in Women With Ovarian Carcinoma. | Norquist BM | JAMA oncology | 2016 | PMID: 26720728 |
Germline mutations in RAD51D confer susceptibility to ovarian cancer. | Loveday C | Nature genetics | 2011 | PMID: 21822267 |
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Text-mined citations for rs587781756 ...
HelpRecord last updated Jun 17, 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.