NM_058216.3(RAD51C):c.397C>A (p.Gln133Lys) AND Fanconi anemia complementation group O

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 8, 2024
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:: RCV000648257.7

Allele description [Variation Report for NM_058216.3(RAD51C):c.397C>A (p.Gln133Lys)]

NM_058216.3(RAD51C):c.397C>A (p.Gln133Lys)

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.397C>A (p.Gln133Lys)

HGVS:

NC_000017.11:g.58695182C>A
NG_023199.1:g.7581C>A
NG_047169.1:g.1898G>T
NM_002876.4:c.397C>A
NM_058216.3:c.397C>AMANE SELECT
NP_002867.1:p.Gln133Lys
NP_478123.1:p.Gln133Lys
LRG_314t1:c.397C>A
LRG_314:g.7581C>A
NC_000017.10:g.56772543C>A
NM_058216.1:c.397C>A
NM_058216.2:c.397C>A
NR_103872.2:n.439C>A
NR_103873.1:n.365C>A

Protein change:

Q133K

Links:

dbSNP: rs387907159

NCBI 1000 Genomes Browser:

rs387907159

Molecular consequence:

NM_002876.4:c.397C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_058216.3:c.397C>A - missense variant - [Sequence Ontology: SO:0001583]
NR_103872.2:n.439C>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_103873.1:n.365C>A - 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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000770071	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 8, 2024)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 26261251, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000770071

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 8, 2024)

germline

clinical testing

PubMed (2)
[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

Contribution of Germline Mutations in the RAD51B, RAD51C, and RAD51D Genes to Ovarian Cancer in the Population.

Song H, Dicks E, Ramus SJ, Tyrer JP, Intermaggio MP, Hayward J, Edlund CK, Conti D, Harrington P, Fraser L, Philpott S, Anderson C, Rosenthal A, Gentry-Maharaj A, Bowtell DD, Alsop K, Cicek MS, Cunningham JM, Fridley BL, Alsop J, Jimenez-Linan M, Høgdall E, et al.

J Clin Oncol. 2015 Sep 10;33(26):2901-7. doi: 10.1200/JCO.2015.61.2408. Epub 2015 Aug 10.

PubMed [citation]

PMID:: 26261251
PMCID:: PMC4554751

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000770071.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change replaces glutamine, which is neutral and polar, with lysine, which is basic and polar, at codon 133 of the RAD51C protein (p.Gln133Lys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with ovarian cancer (PMID: 26261251). ClinVar contains an entry for this variant (Variation ID: 233936). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt RAD51C protein function with a positive predictive value of 80%. 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

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