NM_005591.4(MRE11):c.1492G>A (p.Asp498Asn) AND Ataxia-telangiectasia-like disorder

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Nov 2, 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:: RCV002229550.5

Allele description [Variation Report for NM_005591.4(MRE11):c.1492G>A (p.Asp498Asn)]

NM_005591.4(MRE11):c.1492G>A (p.Asp498Asn)

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.1492G>A (p.Asp498Asn)

HGVS:

NC_000011.10:g.94459416C>T
NG_007261.1:g.39459G>A
NM_001330347.2:c.1492G>A
NM_005590.4:c.1492G>A
NM_005591.4:c.1492G>AMANE SELECT
NP_001317276.1:p.Asp498Asn
NP_005581.2:p.Asp498Asn
NP_005582.1:p.Asp498Asn
NP_005582.1:p.Asp498Asn
LRG_85t1:c.1492G>A
LRG_85:g.39459G>A
LRG_85p1:p.Asp498Asn
NC_000011.9:g.94192582C>T
NM_005591.3:c.1492G>A

Protein change:

D498N

Links:

dbSNP: rs564511708

NCBI 1000 Genomes Browser:

rs564511708

Molecular consequence:

NM_001330347.2:c.1492G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_005590.4:c.1492G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_005591.4:c.1492G>A - missense variant - [Sequence Ontology: SO:0001583]

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
SCV002509595	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Nov 2, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 37013556, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002509595

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Nov 2, 2023)

germline

clinical testing

PubMed (2)
[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

Targeted next-generation sequencing of 21 candidate genes in hereditary ovarian cancer patients from the Republic of Bashkortostan.

Prokofyeva DS, Mingazheva ET, Valova YV, Sakaeva DD, Faishanova RR, Nurgalieva AK, Valiev RR, Bogdanova N, Dörk T, Khusnutdinova EK.

J Ovarian Res. 2023 Apr 4;16(1):66. doi: 10.1186/s13048-023-01119-z.

PubMed [citation]

PMID:: 37013556
PMCID:: PMC10071671

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV002509595.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 498 of the MRE11 protein (p.Asp498Asn). This variant is present in population databases (rs564511708, gnomAD 0.007%). This missense change has been observed in individual(s) with ovarian cancer (PMID: 37013556). ClinVar contains an entry for this variant (Variation ID: 230726). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant¬†is likely to be tolerated. 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	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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