NM_058216.3(RAD51C):c.914G>A (p.Trp305Ter) AND Hereditary cancer-predisposing syndrome

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Sep 8, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000221970.11

Allele description [Variation Report for NM_058216.3(RAD51C):c.914G>A (p.Trp305Ter)]

NM_058216.3(RAD51C):c.914G>A (p.Trp305Ter)

Gene:

RAD51C:RAD51 paralog C [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

17q22

Genomic location:

Preferred name:

NM_058216.3(RAD51C):c.914G>A (p.Trp305Ter)

HGVS:

NC_000017.11:g.58724049G>A
NG_023199.1:g.36448G>A
NM_058216.3:c.914G>AMANE SELECT
NP_478123.1:p.Trp305Ter
LRG_314t1:c.914G>A
LRG_314:g.36448G>A
NC_000017.10:g.56801410G>A
NM_058216.1:c.914G>A
NM_058216.2:c.914G>A
NR_103872.2:n.789G>A

Protein change:

W305*

Links:

dbSNP: rs876659874

NCBI 1000 Genomes Browser:

rs876659874

Molecular consequence:

NR_103872.2:n.789G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_058216.3:c.914G>A - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Hereditary cancer-predisposing syndrome
Synonyms:: Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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CNTN6 [Ailuropoda melanoleuca]
CNTN6 [Ailuropoda melanoleuca]
Gene ID:100480230

Gene
Taxonomy Links for Protein (Select 161986075) (1)
Taxonomy
PMC Links for Protein (Select 161986075) (1)
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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000276789	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Sep 8, 2023)	germline	clinical testing	Citation Link,
SCV001349956	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Nov 16, 2020)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002530032	Sema4, Sema4	criteria provided, single submitter (Sema4 Curation Guidelines)	Pathogenic (Jul 27, 2021)	germline	curation	PubMed (3) [See all records that cite these PMIDs] 30322717, 32809180, 20400964 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000276789

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Sep 8, 2023)

germline

clinical testing

Citation Link,

SCV001349956

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Nov 16, 2020)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV002530032

Sema4, Sema4

criteria provided, single submitter

(Sema4 Curation Guidelines)

Pathogenic
(Jul 27, 2021)

germline

curation

PubMed (3)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing, curation

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Germline pathogenic variants identified in women with ovarian tumors.

Carter NJ, Marshall ML, Susswein LR, Zorn KK, Hiraki S, Arvai KJ, Torene RI, McGill AK, Yackowski L, Murphy PD, Xu Z, Solomon BD, Klein RT, Hruska KS.

Gynecol Oncol. 2018 Dec;151(3):481-488. doi: 10.1016/j.ygyno.2018.09.030. Epub 2018 Oct 12.

PubMed [citation]

PMID:: 30322717

See all PubMed Citations (4)

Details of each submission

From Ambry Genetics, SCV000276789.8

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

The p.W305* pathogenic mutation (also known as c.914G>A), located in coding exon 7 of the RAD51C gene, results from a G to A substitution at nucleotide position 914. This changes the amino acid from a tryptophan to a stop codon within coding exon 7. 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.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Color Diagnostics, LLC DBA Color Health, SCV001349956.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

This variant changes 1 nucleotide in exon 7 of the RAD51C gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in an individual affected with ovarian cancer (PMID: 30322717). This variant has been identified in 1/31390 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.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Sema4, Sema4, SCV002530032.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	curation	PubMed (3)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Oct 26, 2024

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