NM_002875.5(RAD51):c.877G>A (p.Ala293Thr) AND RAD51-related disorders

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Aug 25, 2020
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:: RCV001731668.1

Allele description [Variation Report for NM_002875.5(RAD51):c.877G>A (p.Ala293Thr)]

NM_002875.5(RAD51):c.877G>A (p.Ala293Thr)

Gene:

RAD51:RAD51 recombinase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

15q15.1

Genomic location:

Preferred name:

NM_002875.5(RAD51):c.877G>A (p.Ala293Thr)

HGVS:

NC_000015.10:g.40729955G>A
NG_012120.1:g.39795G>A
NM_001164269.2:c.880G>A
NM_001164270.2:c.774+321G>A
NM_002875.5:c.877G>AMANE SELECT
NM_133487.4:c.880G>A
NP_001157741.1:p.Ala294Thr
NP_002866.2:p.Ala293Thr
NP_597994.3:p.Ala294Thr
LRG_313t1:c.877G>A
LRG_313:g.39795G>A
LRG_313p1:p.Ala293Thr
NC_000015.9:g.41022153G>A
NM_001164269.1:c.880G>A
NM_002875.4:c.877G>A

Protein change:

A293T; ALA293THR

Links:

OMIM: 179617.0005; dbSNP: rs1057519413

NCBI 1000 Genomes Browser:

rs1057519413

Molecular consequence:

NM_001164270.2:c.774+321G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001164269.2:c.880G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_002875.5:c.877G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_133487.4:c.880G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: RAD51-related disorders
Identifiers:

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001984809	Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Aug 25, 2020)	germline	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

SCV001984809

Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Aug 25, 2020)

germline

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	germline	yes	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 Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego, SCV001984809.1

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

Description

This variant has been previously reported as a de novo alteration in a patient with an atypical Fanconi Anemia who presented with growth retardation, microcephaly, hydrocephalus, skeletal (thumb and radius) abnormalities, imperforate anus and an improperly formed left testicle (NM_002875.3: c.877G>A, p.A293T; PMID: 26681308). In vitro characterization of this alteration via functional assays and biochemical studies demonstrated that the variant acts in a dominant-negative manner leading to impaired DNA binding and strand exchange activity as well as impaired ATP hydrolysis. Furthermore, patient's cells were sensitive to DNA crosslinking agents (PMID: 26681308). The c.880G>A p.Ala294Thr variant is absent from the gnomAD population database and thus is presumed to be rare. It affects a highly conserved amino acid and is predicted by multiple in silico tools to have a deleterious effect on protein function. Analysis of the parental samples was negative for the variant, indicating this variant likely occurred as a de novo event. Based on the available evidence, the c.880G>A (p.Ala294Thr) variant is classified as Pathogenic.

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

Last Updated: Mar 10, 2024

ClinVar

Relating variation to medicine