NM_058216.3(RAD51C):c.403T>C (p.Cys135Arg) AND Fanconi anemia complementation group O

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 28, 2023
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV000231632.11

Allele description [Variation Report for NM_058216.3(RAD51C):c.403T>C (p.Cys135Arg)]

NM_058216.3(RAD51C):c.403T>C (p.Cys135Arg)

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.403T>C (p.Cys135Arg)

HGVS:

NC_000017.11:g.58695188T>C
NG_023199.1:g.7587T>C
NG_047169.1:g.1892A>G
NM_002876.4:c.403T>C
NM_058216.3:c.403T>CMANE SELECT
NP_002867.1:p.Trp135Arg
NP_478123.1:p.Cys135Arg
LRG_314t1:c.403T>C
LRG_314:g.7587T>C
NC_000017.10:g.56772549T>C
NM_058216.1:c.403T>C
NM_058216.2:c.403T>C
NR_103872.2:n.445T>C
NR_103873.1:n.371T>C

Protein change:

C135R

Links:

dbSNP: rs878855178

NCBI 1000 Genomes Browser:

rs878855178

Molecular consequence:

NM_002876.4:c.403T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_058216.3:c.403T>C - missense variant - [Sequence Ontology: SO:0001583]
NR_103872.2:n.445T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_103873.1:n.371T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Fanconi anemia complementation group O
Identifiers:: MONDO: MONDO:0013248; MedGen: C3150653; Orphanet: 84; OMIM: 613390

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000291222	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 28, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 30093976, 28864920, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000291222

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 28, 2023)

germline

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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Clinical genetic testing outcome with multi-gene panel in Asian patients with multiple primary cancers.

Chan GHJ, Ong PY, Low JJH, Kong HL, Ow SGW, Tan DSP, Lim YW, Lim SE, Lee SC.

Oncotarget. 2018 Jul 17;9(55):30649-30660. doi: 10.18632/oncotarget.25769.

PubMed [citation]

PMID:: 30093976
PMCID:: PMC6078133

Discovery of mutations in homologous recombination genes in African-American women with breast cancer.

Ding YC, Adamson AW, Steele L, Bailis AM, John EM, Tomlinson G, Neuhausen SL.

Fam Cancer. 2018 Apr;17(2):187-195. doi: 10.1007/s10689-017-0036-4.

PubMed [citation]

PMID:: 28864920
PMCID:: PMC5834346

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000291222.9

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

Description

This sequence change replaces cysteine, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 135 of the RAD51C protein (p.Cys135Arg). This variant is present in population databases (no rsID available, gnomAD 0.003%). This missense change has been observed in individual(s) with breast cancer and ovarian cancer (PMID: 28864920, 30093976). ClinVar contains an entry for this variant (Variation ID: 241771). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Experimental studies have shown that this missense change affects RAD51C function (PMID: 28864920). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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: Sep 29, 2024

ClinVar

Relating variation to medicine