VCV000031557.29 - ClinVar

NM_058216.3(RAD51C):c.230del (p.Gly77fs)

Germline

Classification

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.

(5)

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

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.230del (p.Gly77fs)

Variation ID: 31557 Accession: VCV000031557.29

Type and length

Deletion, 1 bp

Location

Cytogenetic: 17q22 17: 58695014 (GRCh38) [ NCBI UCSC ] 17: 56772375 (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	Sep 13, 2013	May 1, 2024	Feb 6, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_058216.3:c.230del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_478123.1:p.Gly77fs	frameshift
NM_058216.3:c.230delG MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NM_002876.4:c.230del	NP_002867.1:p.Gly77fs	frameshift
NM_058216.1:c.230del
NR_103872.2:n.272del		non-coding transcript variant
NR_103873.1:n.198del		non-coding transcript variant
NC_000017.11:g.58695015del
NC_000017.10:g.56772376del
NG_023199.1:g.7414del
NG_047169.1:g.2066del
LRG_314:g.7414del
LRG_314t1:c.230del

... more HGVS ... less HGVS

Protein change

G77fs

Other names

Canonical SPDI

NC_000017.11:58695013:GG:G

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The 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

ClinGen: CA16044116 LOVD 3: RAD51C_000003 OMIM: 602774.0006 dbSNP: rs1057519355 VarSome

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
Gene	OMIM	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	1857	2066

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.
Breast-ovarian cancer, familial, susceptibility to, 3	Pathogenic; risk factor (2)	no assertion criteria provided	Aug 26, 2022	RCV000024265.5
Ovarian neoplasm	Pathogenic (1)	no assertion criteria provided	Feb 28, 2020	RCV001195013.1
Hereditary cancer-predisposing syndrome	Pathogenic (1)	criteria provided, single submitter	May 26, 2023	RCV001015159.4
not provided	Pathogenic (1)	criteria provided, single submitter	Feb 6, 2024	RCV003493412.1

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 (Feb 06, 2024)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital Accession: SCV004242883.1 First in ClinVar: Feb 14, 2024 Last updated: Feb 14, 2024
Pathogenic (May 26, 2023)	criteria provided, single submitter (Ambry Variant Classification Scheme 2023) Method: clinical testing	Hereditary cancer-predisposing syndrome Affected status: unknown Allele origin: germline	Ambry Genetics Accession: SCV001175966.5 First in ClinVar: Mar 16, 2020 Last updated: May 01, 2024	Publications: PubMed (1) PubMed: 21990120 Comment: The c.230delG pathogenic mutation, located in coding exon 2 of the RAD51C gene, results from a deletion of one nucleotide at nucleotide position 230, causing … (more) The c.230delG pathogenic mutation, located in coding exon 2 of the RAD51C gene, results from a deletion of one nucleotide at nucleotide position 230, causing a translational frameshift with a predicted alternate stop codon (p.G77Vfs*24). This variant has been reported in a patient with high-grade serous ovarian cancer and metachronous breast cancer; her ovarian tumor showed loss of the wild type allele (Thompson ER et al. Hum. Mutat., 2012 Jan;33:95-9). 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)
risk factor (Jan 01, 2012)	no assertion criteria provided Method: literature only	BREAST-OVARIAN CANCER, FAMILIAL, SUSCEPTIBILITY TO, 3 Affected status: not provided Allele origin: germline	OMIM Accession: SCV000045556.3 First in ClinVar: Apr 04, 2013 Last updated: Sep 08, 2019	Publications: PubMed (1) PubMed: 21990120 Comment on evidence: In a patient with breast-ovarian cancer-3 (613399), Thompson et al. (2012) identified a heterozygous 1-bp deletion (230delG) in exon 2 of the RAD51C gene, resulting … (more) In a patient with breast-ovarian cancer-3 (613399), Thompson et al. (2012) identified a heterozygous 1-bp deletion (230delG) in exon 2 of the RAD51C gene, resulting in a frameshift and premature termination (Gly77ValfsTer24). The mutation was not found in 427 controls. No family history was available. (less)
Pathogenic (Feb 28, 2020)	no assertion criteria provided Method: curation	Ovarian cancer Affected status: yes Allele origin: germline	Leiden Open Variation Database Accession: SCV001365251.1 First in ClinVar: Jun 28, 2020 Last updated: Jun 28, 2020	Publications: PubMed (1) PubMed: 21990120 Comment: Curator: Arleen D. Auerbach. Submitter to LOVD: Ian Campbell.
Pathogenic (Aug 26, 2022)	no assertion criteria provided Method: clinical testing	Breast-ovarian cancer, familial, susceptibility to, 3 Affected status: yes Allele origin: germline	BRCAlab, Lund University Accession: SCV002589009.1 First in ClinVar: Apr 01, 2023 Last updated: Apr 01, 2023

Comment:

The c.230delG pathogenic mutation, located in coding exon 2 of the RAD51C gene, results from a deletion of one nucleotide at nucleotide position 230, causing a translational frameshift with a predicted alternate stop codon (p.G77Vfs*24). This variant has been reported in a patient with high-grade serous ovarian cancer and metachronous breast cancer; her ovarian tumor showed loss of the wild type allele (Thompson ER et al. Hum. Mutat., 2012 Jan;33:95-9). 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.

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:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Analysis of RAD51C germline mutations in high-risk breast and ovarian cancer families and ovarian cancer patients.	Thompson ER	Human mutation	2012	PMID: 21990120

Text-mined citations for rs1057519355 ...

These 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 Jul 15, 2024

ClinVar Genomic variation as it relates to human health

NM_058216.3(RAD51C):c.230del (p.Gly77fs)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs1057519355 ...