NM_005591.4(MRE11):c.1897C>T (p.Arg633Ter) AND Ataxia-telangiectasia-like disorder

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 14, 2023
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:: RCV001034660.6

Allele description [Variation Report for NM_005591.4(MRE11):c.1897C>T (p.Arg633Ter)]

NM_005591.4(MRE11):c.1897C>T (p.Arg633Ter)

Gene:

MRE11:MRE11 homolog, double strand break repair nuclease [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

11q21

Genomic location:

Preferred name:

NM_005591.4(MRE11):c.1897C>T (p.Arg633Ter)

HGVS:

NC_000011.10:g.94437206G>A
NG_007261.1:g.61669C>T
NM_001330347.2:c.1894C>T
NM_005590.4:c.1813C>T
NM_005591.4:c.1897C>TMANE SELECT
NP_001317276.1:p.Arg632Ter
NP_005581.2:p.Arg605Ter
NP_005582.1:p.Arg633Ter
NP_005582.1:p.Arg633Ter
LRG_85t1:c.1897C>T
LRG_85:g.61669C>T
LRG_85p1:p.Arg633Ter
NC_000011.9:g.94170372G>A
NM_005591.3:c.1897C>T

Protein change:

R605*; ARG633TER

Links:

OMIM: 600814.0001; dbSNP: rs137852759

NCBI 1000 Genomes Browser:

rs137852759

Molecular consequence:

NM_001330347.2:c.1894C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_005590.4:c.1813C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_005591.4:c.1897C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Ataxia-telangiectasia-like disorder (ATLD)
Identifiers:: MONDO: MONDO:0011457; MedGen: C1858391; OMIM: PS604391

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000832713	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 14, 2023)	germline	clinical testing	PubMed (9) [See all records that cite these PMIDs] 23080121, 23912341, 8445618, 19383352, 22863007, 10612394, 14690604, 25040471, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000832713

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 14, 2023)

germline

clinical testing

PubMed (9)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

Mre11 ATLD17/18 mutation retains Tel1/ATM activity but blocks DNA double-strand break repair.

Limbo O, Moiani D, Kertokalio A, Wyman C, Tainer JA, Russell P.

Nucleic Acids Res. 2012 Dec;40(22):11435-49. doi: 10.1093/nar/gks954. Epub 2012 Oct 17.

PubMed [citation]

PMID:: 23080121
PMCID:: PMC3526295

Disease-associated MRE11 mutants impact ATM/ATR DNA damage signaling by distinct mechanisms.

Regal JA, Festerling TA, Buis JM, Ferguson DO.

Hum Mol Genet. 2013 Dec 20;22(25):5146-59. doi: 10.1093/hmg/ddt368. Epub 2013 Aug 2.

PubMed [citation]

PMID:: 23912341
PMCID:: PMC3842175

See all PubMed Citations (9)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000832713.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (9)

Description

This sequence change creates a premature translational stop signal (p.Arg633*) in the MRE11 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MRE11 are known to be pathogenic (PMID: 23080121, 23912341). This variant is present in population databases (rs137852759, gnomAD 0.02%). This premature translational stop signal has been observed in individual(s) with ataxia-telangiectasia-like disorder, nephronophthisis-related ciliopathies and/or breast cancer (PMID: 8445618, 10612394, 19383352, 22863007). ClinVar contains an entry for this variant (Variation ID: 8782). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies have shown that this premature translational stop signal affects MRE11 function (PMID: 10612394, 14690604, 25040471). For these reasons, this variant has been classified as Pathogenic.

#	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

Last Updated: Sep 29, 2024

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