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NM_000051.3(ATM):c.8147T>C (p.Val2716Ala) AND not provided

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Apr 20, 2018
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:

Allele description

NM_000051.3(ATM):c.8147T>C (p.Val2716Ala)

ATM:ATM serine/threonine kinase [Gene - OMIM - HGNC]
C11orf65:chromosome 11 open reading frame 65 [Gene - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Genomic location:
Preferred name:
NM_000051.3(ATM):c.8147T>C (p.Val2716Ala)
Other names:
  • NC_000011.10:g.108335105T>C
  • NG_009830.1:g.117274T>C
  • NG_054724.1:g.139728A>G
  • NM_000051.3:c.8147T>C
  • NM_001330368.2:c.641-26034A>G
  • NM_001351110.2:c.38+115A>G
  • NM_001351834.2:c.8147T>C
  • NP_000042.3:p.Val2716Ala
  • NP_000042.3:p.Val2716Ala
  • NP_001338763.1:p.Val2716Ala
  • LRG_135t1:c.8147T>C
  • LRG_135:g.117274T>C
  • LRG_135p1:p.Val2716Ala
  • NC_000011.9:g.108205832T>C
  • p.V2716A
Protein change:
dbSNP: rs587782652
NCBI 1000 Genomes Browser:
Molecular consequence:
  • NM_001330368.2:c.641-26034A>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001351110.2:c.38+115A>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000051.3:c.8147T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001351834.2:c.8147T>C - missense variant - [Sequence Ontology: SO:0001583]


MedGen: CN517202

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Assertion and evidence details

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

(GeneDx Variant Classification (06012015))
(Apr 20, 2018)
germlineclinical testing

Citation Link

Summary from all submissions

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

Details of each submission

From GeneDx, SCV000209770.13

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided


This variant is denoted ATM c.8147T>C at the cDNA level, p.Val2716Ala (V2716A) at the protein level, and results in the change of a Valine to an Alanine (GTT>GCT). This variant has been observed in the compound heterozygous state in multiple individuals with atypical or later-onset ataxia telangiectasia (Hiel 2006, Verhagen 2009, Demuth 2011, Keimling 2011, M?neret 2014, Kuhm 2015, Lohmann 2015, van Os 2017). In addition, ATM Val2716Ala has been published in the heterozygous state in at least three individuals with early-onset breast cancer, one of whom also had a history of unexplained childhood onset choreoathetosis, oculocutaneous telangiectasias, and elevated serum alpha-fetoprotein (Mandigers 2011, Reiman 2011). Although this variant may express some level of kinase activity, it has been associated with reduced ATM protein expression, and transfected cells have exhibited reduced radiation-induced kinase activity (Scott 2002, Verhagen 2009, Demuth 2011, Reiman 2011). ATM Val2716Ala was not observed at a significant allele frequency in large population cohorts (Lek 2016). This variant is located in the kinase domain and the ATP-binding domain (Lavin 2004, Stracker 2013). In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect. Based on currently available evidence, we consider ATM Val2716Ala to be pathogenic.

OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Jan 17, 2021