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NM_000051.4(ATM):c.7559T>G (p.Met2520Arg) AND Ataxia-telangiectasia syndrome

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Nov 13, 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:
RCV000627852.16

Allele description [Variation Report for NM_000051.4(ATM):c.7559T>G (p.Met2520Arg)]

NM_000051.4(ATM):c.7559T>G (p.Met2520Arg)

Genes:
ATM:ATM serine/threonine kinase [Gene - OMIM - HGNC]
C11orf65:chromosome 11 open reading frame 65 [Gene - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
11q22.3
Genomic location:
Preferred name:
NM_000051.4(ATM):c.7559T>G (p.Met2520Arg)
HGVS:
  • NC_000011.10:g.108331487T>G
  • NG_009830.1:g.113656T>G
  • NG_054724.1:g.143346A>C
  • NM_000051.4:c.7559T>GMANE SELECT
  • NM_001330368.2:c.641-22416A>C
  • NM_001351110.2:c.*38+3733A>C
  • NM_001351834.2:c.7559T>G
  • NM_152587.2:c.*1350A>C
  • NP_000042.3:p.Met2520Arg
  • NP_000042.3:p.Met2520Arg
  • NP_001338763.1:p.Met2520Arg
  • LRG_135t1:c.7559T>G
  • LRG_135:g.113656T>G
  • LRG_135p1:p.Met2520Arg
  • NC_000011.9:g.108202214T>G
  • NM_000051.3:c.7559T>G
  • NR_147053.3:n.2453A>C
  • p.M2520R
Protein change:
M2520R
Links:
dbSNP: rs587782692
NCBI 1000 Genomes Browser:
rs587782692
Molecular consequence:
  • NM_001330368.2:c.641-22416A>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001351110.2:c.*38+3733A>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000051.4:c.7559T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001351834.2:c.7559T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NR_147053.3:n.2453A>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:
Ataxia-telangiectasia syndrome (AT)
Synonyms:
Louis-Bar syndrome; Cerebello-oculocutaneous telangiectasia; Immunodeficiency with ataxia telangiectasia; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0008840; MedGen: C0004135; Orphanet: 100; OMIM: 208900

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000748736Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Pathogenic
(Nov 13, 2023)
germlineclinical testing

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

Summary from all submissions

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

Citations

PubMed

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, SCV000748736.7

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

Description

This sequence change replaces methionine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 2520 of the ATM protein (p.Met2520Arg). RNA analysis indicates that this missense change induces altered splicing and may result in an absent or disrupted protein product. This variant is present in population databases (rs587782692, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with ATM-related conditions. ClinVar contains an entry for this variant (Variation ID: 142749). 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 disruptive. Studies have shown that this missense change results in activation of a cryptic splice site and introduces a premature termination codon (Invitae). The resulting mRNA is expected to undergo nonsense-mediated decay. For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: Feb 8, 2025