NM_058216.3(RAD51C):c.630T>G (p.Tyr210Ter) AND not provided

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Jun 22, 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:: RCV000657719.3

Allele description [Variation Report for NM_058216.3(RAD51C):c.630T>G (p.Tyr210Ter)]

NM_058216.3(RAD51C):c.630T>G (p.Tyr210Ter)

Genes:

LOC129390903:MPRA-validated peak2919 silencer [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.630T>G (p.Tyr210Ter)

HGVS:

NC_000017.11:g.58703254T>G
NG_023199.1:g.15653T>G
NM_058216.3:c.630T>GMANE SELECT
NP_478123.1:p.Tyr210Ter
LRG_314t1:c.630T>G
LRG_314:g.15653T>G
NC_000017.10:g.56780615T>G
NM_058216.1:c.630T>G
NM_058216.2:c.630T>G
NR_103872.2:n.505T>G
p.Y210*

Protein change:

Y210*

Links:

dbSNP: rs786201909

NCBI 1000 Genomes Browser:

rs786201909

Molecular consequence:

NR_103872.2:n.505T>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_058216.3:c.630T>G - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000779468	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Pathogenic (Nov 7, 2018)	germline	clinical testing	Citation Link,
SCV004220150	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Pathogenic (Jun 22, 2023)	unknown	clinical testing	PubMed (3) [See all records that cite these PMIDs] 30128536, 28152038, 26467025

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000779468

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Pathogenic
(Nov 7, 2018)

germline

clinical testing

Citation Link,

SCV004220150

Quest Diagnostics Nichols Institute San Juan Capistrano

criteria provided, single submitter

(Quest Diagnostics criteria)

Pathogenic
(Jun 22, 2023)

unknown

clinical testing

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

Help

Summary from all submissions

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

Citations

PubMed

Association of Breast and Ovarian Cancers With Predisposition Genes Identified by Large-Scale Sequencing.

Lu HM, Li S, Black MH, Lee S, Hoiness R, Wu S, Mu W, Huether R, Chen J, Sridhar S, Tian Y, McFarland R, Dolinsky J, Tippin Davis B, Mexal S, Dunlop C, Elliott A.

JAMA Oncol. 2019 Jan 1;5(1):51-57. doi: 10.1001/jamaoncol.2018.2956. Erratum in: JAMA Oncol. 2019 Jan 1;5(1):122. doi: 10.1001/jamaoncol.2018.6918.

PubMed [citation]

PMID:: 30128536
PMCID:: PMC6439764

Exome sequencing covers >98% of mutations identified on targeted next generation sequencing panels.

LaDuca H, Farwell KD, Vuong H, Lu HM, Mu W, Shahmirzadi L, Tang S, Chen J, Bhide S, Chao EC.

PLoS One. 2017;12(2):e0170843. doi: 10.1371/journal.pone.0170843.

PubMed [citation]

PMID:: 28152038
PMCID:: PMC5289469

See all PubMed Citations (3)

Details of each submission

From GeneDx, SCV000779468.2

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

Description

This variant is denoted RAD51C c.630T>G at the cDNA level and p.Tyr210Ter (Y210X) at the protein level. The substitution creates a nonsense variant, which changes a Tyrosine to a premature stop codon (TAT>TAG), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant has been observed in at least one individual undergoing multi-gene panel testing (LaDuca 2017) and is considered pathogenic.

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

From Quest Diagnostics Nichols Institute San Juan Capistrano, SCV004220150.1

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

Description

The RAD51C c.630T>G (p.Tyr210*) variant causes the premature termination of RAD51C protein synthesis. This variant has been reported in the published literature in an individual with ovarian cancer (PMID: 30128536 (2018)). This variant has not been reported in large, multi-ethnic general populations (Genome Aggregation Database, http://gnomad.broadinstitute.org). Based on the available information, this variant is classified as pathogenic.

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

Last Updated: Sep 29, 2024

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