NM_058216.3(RAD51C):c.492T>G (p.Phe164Leu) AND Fanconi anemia complementation group O

Germline classification:: Uncertain significance (3 submissions)
Last evaluated:: Jan 19, 2024
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:: RCV000168314.22

Allele description [Variation Report for NM_058216.3(RAD51C):c.492T>G (p.Phe164Leu)]

NM_058216.3(RAD51C):c.492T>G (p.Phe164Leu)

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.492T>G (p.Phe164Leu)

HGVS:

NC_000017.11:g.58696780T>G
NG_023199.1:g.9179T>G
NG_047169.1:g.300A>C
NM_058216.3:c.492T>GMANE SELECT
NP_478123.1:p.Phe164Leu
LRG_314t1:c.492T>G
LRG_314:g.9179T>G
NC_000017.10:g.56774141T>G
NM_058216.1:c.492T>G
NM_058216.2:c.492T>G

Protein change:

F164L

Links:

dbSNP: rs573992101

NCBI 1000 Genomes Browser:

rs573992101

Molecular consequence:

NM_058216.3:c.492T>G - missense variant - [Sequence Ontology: SO:0001583]

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
SCV000218998	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 19, 2024)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 28528518, 28492532
SCV000490089	Counsyl	criteria provided, single submitter (Counsyl Autosomal Dominant Disease Classification criteria (2015))	Uncertain significance (Nov 2, 2016)	unknown	clinical testing	Counsyl Autosomal Dominant Disease Classification criteria (2015), Citation Link,
SCV001482821	Baylor Genetics - CSER-TexasKidsCanSeq	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Jun 22, 2020)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000218998

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 19, 2024)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

SCV000490089

Counsyl

criteria provided, single submitter

(Counsyl Autosomal Dominant Disease Classification criteria (2015))

Uncertain significance
(Nov 2, 2016)

unknown

clinical testing

Counsyl Autosomal Dominant Disease Classification criteria (2015),

Citation Link,

SCV001482821

Baylor Genetics - CSER-TexasKidsCanSeq

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Jun 22, 2020)

unknown

clinical testing

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

Help

Summary from all submissions

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

Citations

PubMed

A multi-gene panel study in hereditary breast and ovarian cancer in Colombia.

Cock-Rada AM, Ossa CA, Garcia HI, Gomez LR.

Fam Cancer. 2018 Jan;17(1):23-30. doi: 10.1007/s10689-017-0004-z.

PubMed [citation]

PMID:: 28528518

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

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000218998.12

#	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 phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 164 of the RAD51C protein (p.Phe164Leu). This variant is present in population databases (rs573992101, gnomAD 0.02%). This missense change has been observed in individual(s) with breast cancer and/or ovarian cancer (PMID: 28528518). ClinVar contains an entry for this variant (Variation ID: 188317). 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 not expected to disrupt RAD51C protein function with a negative 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

From Counsyl, SCV000490089.2

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

#	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

From Baylor Genetics - CSER-TexasKidsCanSeq, SCV001482821.1

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

Description

This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].

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

Last Updated: Nov 18, 2024

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