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NM_005591.4(MRE11):c.658A>C (p.Arg220=) AND Ataxia-telangiectasia-like disorder

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Jul 1, 2021
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:
RCV002239143.2

Allele description

NM_005591.4(MRE11):c.658A>C (p.Arg220=)

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.658A>C (p.Arg220=)
HGVS:
  • NC_000011.10:g.94476290T>G
  • NG_007261.1:g.22585A>C
  • NM_001330347.2:c.658A>C
  • NM_005590.4:c.658A>C
  • NM_005591.4:c.658A>CMANE SELECT
  • NP_001317276.1:p.Arg220=
  • NP_005581.2:p.Arg220=
  • NP_005582.1:p.Arg220=
  • LRG_85:g.22585A>C
  • NC_000011.9:g.94209456T>G
Links:
dbSNP: rs764827899
NCBI 1000 Genomes Browser:
rs764827899
Molecular consequence:
  • NM_001330347.2:c.658A>C - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_005590.4:c.658A>C - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_005591.4:c.658A>C - synonymous variant - [Sequence Ontology: SO:0001819]

Condition(s)

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

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002509517Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Jul 1, 2021) 		germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

Two unrelated patients with MRE11A mutations and Nijmegen breakage syndrome-like severe microcephaly.

Matsumoto Y, Miyamoto T, Sakamoto H, Izumi H, Nakazawa Y, Ogi T, Tahara H, Oku S, Hiramoto A, Shiiki T, Fujisawa Y, Ohashi H, Sakemi Y, Matsuura S.

DNA Repair (Amst). 2011 Mar 7;10(3):314-21. doi: 10.1016/j.dnarep.2010.12.002. Epub 2011 Jan 12.

PubMed [citation]
PMID:
21227757

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV002509517.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

This sequence change affects codon 220 of the MRE11 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the MRE11 protein. RNA analysis indicates that this variant induces altered splicing and may result in an absent or disrupted protein product. This variant is present in population databases (rs764827899, ExAC 0.02%). This variant has been observed in individual(s) with Nijmegen breakage syndrome-like severe microcephaly (PMID: 21227757). Studies have shown that this variant results in skipping of exon 7, which introduces a premature termination codon (PMID: 21227757). The resulting mRNA is expected to undergo nonsense-mediated decay. 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.

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

Last Updated: Dec 24, 2023