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NM_000051.4(ATM):c.6115G>A (p.Glu2039Lys) AND ATM-related disorder

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Jan 13, 2024
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:
RCV004547473.1

Allele description [Variation Report for NM_000051.4(ATM):c.6115G>A (p.Glu2039Lys)]

NM_000051.4(ATM):c.6115G>A (p.Glu2039Lys)

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.6115G>A (p.Glu2039Lys)
HGVS:
  • NC_000011.10:g.108316030G>A
  • NG_009830.1:g.98199G>A
  • NG_054724.1:g.158803C>T
  • NM_000051.4:c.6115G>AMANE SELECT
  • NM_001330368.2:c.641-6959C>T
  • NM_001351110.2:c.*39-6959C>T
  • NM_001351834.2:c.6115G>A
  • NP_000042.3:p.Glu2039Lys
  • NP_000042.3:p.Glu2039Lys
  • NP_001338763.1:p.Glu2039Lys
  • LRG_135t1:c.6115G>A
  • LRG_135:g.98199G>A
  • LRG_135p1:p.Glu2039Lys
  • NC_000011.9:g.108186757G>A
  • NM_000051.3:c.6115G>A
Protein change:
E2039K
Links:
dbSNP: rs864622251
NCBI 1000 Genomes Browser:
rs864622251
Molecular consequence:
  • NM_001330368.2:c.641-6959C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001351110.2:c.*39-6959C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000051.4:c.6115G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001351834.2:c.6115G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
ATM-related disorder
Synonyms:
ATM-related disorders; ATM-related condition
Identifiers:

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV004721134PreventionGenetics, part of Exact Sciences
criteria provided, single submitter

(ACMG Guidelines, 2015)
Likely pathogenic
(Jan 13, 2024)
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

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 PreventionGenetics, part of Exact Sciences, SCV004721134.1

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

Description

The ATM c.6115G>A variant is predicted to result in the amino acid substitution p.Glu2039Lys. This variant has been observed in multiple individuals with breast cancer (Table S2 - Tavtigian et al. 2009. PubMed ID: 19781682; Table S4 - Siraj et al. 2017. PubMed ID: 28975465). Additionally, this variant has been reported with another variant in the compound heterozygous state in an individual with ataxia-telangiectasia (Jacquemin et al. 2012. PubMed ID: 22071889). Functional studies demonstrated reduced kinase activity (Barone et al. 2009. PubMed ID: 19431188) and defective response to ionizing radiation (Jacquemin et al. 2012. PubMed ID: 22071889). This variant is reported in 0.0033% of alleles in individuals of South Asian descent in gnomAD and has conflicting interpretations of pathogenicity of uncertain and likely pathogenic in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/219787/). This variant is interpreted as likely pathogenic.

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

Last Updated: Jul 15, 2024