NM_058216.3(RAD51C):c.406A>T (p.Met136Leu) AND Breast-ovarian cancer, familial, susceptibility to, 3

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Jul 4, 2023
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:: RCV003239288.2

Allele description [Variation Report for NM_058216.3(RAD51C):c.406A>T (p.Met136Leu)]

NM_058216.3(RAD51C):c.406A>T (p.Met136Leu)

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.406A>T (p.Met136Leu)

Other names:

p.M136L:ATG>TTG

HGVS:

NC_000017.11:g.58696694A>T
NG_023199.1:g.9093A>T
NG_047169.1:g.386T>A
NM_058216.3:c.406A>TMANE SELECT
NP_478123.1:p.Met136Leu
LRG_314t1:c.406A>T
LRG_314:g.9093A>T
NC_000017.10:g.56774055A>T
NM_058216.1:c.406A>T
NM_058216.2:c.406A>T

Protein change:

M136L

Links:

dbSNP: rs587780254

NCBI 1000 Genomes Browser:

rs587780254

Molecular consequence:

NM_058216.3:c.406A>T - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Breast-ovarian cancer, familial, susceptibility to, 3
Synonyms:: RAD51C-Related Breast/Ovarian Cancer; Breast-ovarian cancer, familial 3
Identifiers:: MONDO: MONDO:0013253; MedGen: C3150659; Orphanet: 145; OMIM: 613399

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mitochondrial arginine transporter BAC1 isoform X1 [Ziziphus jujuba]
mitochondrial arginine transporter BAC1 isoform X1 [Ziziphus jujuba]
gi|1009109489|ref|XP_015890487.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003936125	KCCC/NGS Laboratory, Kuwait Cancer Control Center	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Jul 4, 2023)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004207990	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Jun 16, 2023)	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

SCV003936125

KCCC/NGS Laboratory, Kuwait Cancer Control Center

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Jul 4, 2023)

unknown

clinical testing

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

SCV004207990

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Jun 16, 2023)

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	1	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

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From KCCC/NGS Laboratory, Kuwait Cancer Control Center, SCV003936125.1

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

Description

This sequence change replaces methionine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 136 of the RAD51C protein (p.Met136Leu). This variant is present in population databases (rs587780254, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with RAD51C-related conditions.Five ClinVar submitters (evaluation after 2014) cite the variant as uncertain significance (Variation ID: 128204). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated and.computational tools predict no significant impact on normal splicing. 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	unknown	yes	not provided	not provided	not provided		1	not provided	not provided	not provided

From Baylor Genetics, SCV004207990.1

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

#	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

Last Updated: Sep 29, 2024

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