NM_002878.4(RAD51D):c.355T>C (p.Cys119Arg) AND Malignant tumor of breast

Clinical significance:Uncertain significance

Review status:(0/4) 0 stars out of maximum of 4 stars

no assertion criteria provided

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001354078.1

Allele description [Variation Report for NM_002878.4(RAD51D):c.355T>C (p.Cys119Arg)]

NM_002878.4(RAD51D):c.355T>C (p.Cys119Arg)

Genes:
RAD51D:RAD51 paralog D [Gene - OMIM - HGNC]
RAD51L3-RFFL:RAD51L3-RFFL readthrough [Gene]
Variant type:
single nucleotide variant
Cytogenetic location:
17q12
Genomic location:
Preferred name:
NM_002878.4(RAD51D):c.355T>C (p.Cys119Arg)
Other names:
p.C119R:TGT>CGT
HGVS:
  • NC_000017.11:g.35107113A>G
  • NG_031858.1:g.17757T>C
  • NM_001142571.2:c.415T>C
  • NM_002878.3:c.355T>C
  • NM_002878.4:c.355T>CMANE SELECT
  • NM_133629.3:c.145-632T>C
  • NP_001136043.1:p.Cys139Arg
  • NP_002869.3:p.Cys119Arg
  • NP_002869.3:p.Cys119Arg
  • LRG_516t1:c.355T>C
  • LRG_516:g.17757T>C
  • LRG_516p1:p.Cys119Arg
  • NC_000017.10:g.33434132A>G
  • NR_037711.2:n.381T>C
  • p.C119R
Protein change:
C119R
Links:
dbSNP: rs201313861
NCBI 1000 Genomes Browser:
rs201313861
Molecular consequence:
  • NM_133629.3:c.145-632T>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001142571.2:c.415T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_002878.3:c.355T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_002878.4:c.355T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NR_037711.2:n.381T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:
Malignant tumor of breast
Synonyms:
Breast cancer; Malignant breast neoplasm
Identifiers:
MONDO: MONDO:0007254; MedGen: C0006142

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001548605Department of Pathology and Laboratory Medicine,Sinai Health System - The Canadian Open Genetics Repository (COGR)

See additional submitters

no assertion criteria providedUncertain significanceunknownclinical testing

Summary from all submissions

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

Details of each submission

From Department of Pathology and Laboratory Medicine,Sinai Health System - The Canadian Open Genetics Repository (COGR), SCV001548605.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The RAD51D p.Cys119Arg variant was identified in 4 of 8892 proband chromosomes (frequency: 0.0004) from individuals or families with breast and ovarian cancer and was present in 2 of 5544 control chromosomes (frequency: 0.0004) from healthy individuals (Gutierrez-Enriquez 2013, Osher 2012, Song 2015). The variant was also identified in dbSNP (ID: rs201313861) as “With Uncertain significance allele”, and in ClinVar (classified as uncertain significance by GeneDx, Ambry genetics, Invitae, LCOA clinical laboratory). The variant was not identified in the Cosmic database. The variant was identified in control databases in 15 of 277134 chromosomes at a frequency of 0.0001 (Genome Aggregation Database Feb 27, 2017). It was observed in the following populations: African in 1 of 24020 chromosomes (freq: 0.00004), Latino in 3 of 34420 chromosomes (freq: 0.0001), European in 11 of 126692 chromosomes (freq: 0.0001); it was not observed in the “Other”, Ashkenazi Jewish, East Asian, Finnish, and South Asian populations. The p.Cys119 residue is conserved in mammals and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) provide inconsistent predictions regarding the impact to the protein; this information is not very predictive of pathogenicity. The variant occurs outside of the splicing consensus sequence and 1 of 5 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) predict a greater than 10% difference in splicing; this is not very predictive of pathogenicity. In summary, based on the above information, the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance.

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

Last Updated: Nov 27, 2021

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