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NM_058216.3(RAD51C):c.106G>A (p.Glu36Lys) AND Hereditary cancer-predisposing syndrome

Germline classification:
Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:
Sep 8, 2023
Review status:
criteria provided, conflicting classifications
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:
RCV000569780.9

Allele description [Variation Report for NM_058216.3(RAD51C):c.106G>A (p.Glu36Lys)]

NM_058216.3(RAD51C):c.106G>A (p.Glu36Lys)

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.106G>A (p.Glu36Lys)
HGVS:
  • NC_000017.11:g.58692749G>A
  • NG_023199.1:g.5148G>A
  • NG_047169.1:g.4331C>T
  • NM_002876.4:c.106G>A
  • NM_058216.3:c.106G>AMANE SELECT
  • NP_002867.1:p.Glu36Lys
  • NP_478123.1:p.Glu36Lys
  • LRG_314t1:c.106G>A
  • LRG_314:g.5148G>A
  • NC_000017.10:g.56770110G>A
  • NM_058216.1:c.106G>A
  • NM_058216.2:c.106G>A
  • NR_103872.2:n.148G>A
Protein change:
E36K
Links:
dbSNP: rs773998134
NCBI 1000 Genomes Browser:
rs773998134
Molecular consequence:
  • NM_002876.4:c.106G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_058216.3:c.106G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NR_103872.2:n.148G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

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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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000667108Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Uncertain significance
(Sep 8, 2023) 		germlineclinical testing

PubMed (7)
[See all records that cite these PMIDs]

Citation Link,

SCV000911102Color Diagnostics, LLC DBA Color Health
criteria provided, single submitter

(ACMG Guidelines, 2015)		Likely benign
(Jul 18, 2016) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

A HRM-based screening method detects RAD51C germ-line deleterious mutations in Spanish breast and ovarian cancer families.

Romero A, Pérez-Segura P, Tosar A, García-Saenz JA, Díaz-Rubio E, Caldés T, de la Hoya M.

Breast Cancer Res Treat. 2011 Oct;129(3):939-46. doi: 10.1007/s10549-011-1543-x. Epub 2011 May 3.

PubMed [citation]
PMID:
21537932

Predominance of pathogenic missense variants in the RAD51C gene occurring in breast and ovarian cancer families.

Osorio A, Endt D, Fernández F, Eirich K, de la Hoya M, Schmutzler R, Caldés T, Meindl A, Schindler D, Benitez J.

Hum Mol Genet. 2012 Jul 1;21(13):2889-98. doi: 10.1093/hmg/dds115. Epub 2012 Mar 26.

PubMed [citation]
PMID:
22451500
See all PubMed Citations (8)

Details of each submission

From Ambry Genetics, SCV000667108.6

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (7)

Description

The p.E36K variant (also known as c.106G>A), located in coding exon 1 of the RAD51C gene, results from a G to A substitution at nucleotide position 106. The glutamic acid at codon 36 is replaced by lysine, an amino acid with similar properties. This alteration was originally identified in a Spanish female diagnosed with breast cancer at age 38 who had two relatives with breast cancer (Romero A et al. Breast Cancer Res. Treat. 2011 Oct;129(3):939-46). This cohort was later included with other Spanish breast and/or ovarian cancer families, and p.E36K was ultimately reported in 1/785 affected families (Osorio A et al. Hum. Mol. Genet. 2012 Jul;21(13):2889-98). This variant was also reported in 2/142 unrelated patients with breast and/or ovarian cancer who had either early onset cancer or a family history of breast/ovarian cancer (Goldmar L et al. BMC Cancer. 2013;13:484), and also reported in 1/34 Italian breast cancer patients (Guacci A et al. J Clin Lab Anal, 2018 Jul;32:e22418). In a homology-directed DNA repair (HDR) assay, this alteration showed a functionally normal read-out. (Hu C et al. Cancer Res, 2023 Aug;83:2557-2571). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Color Diagnostics, LLC DBA Color Health, SCV000911102.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024