NM_000051.3(ATM):c.8562C>T (p.Arg2854=) AND not specified

Clinical significance:Conflicting interpretations of pathogenicity, Likely benign(1);Uncertain significance(1) (Last evaluated: Mar 30, 2018)

Review status:1 star out of maximum of 4 stars

criteria provided, conflicting interpretations

Based on:
2 submissions [Details]
Record status:

Allele description [Variation Report for NM_000051.3(ATM):c.8562C>T (p.Arg2854=)]

NM_000051.3(ATM):c.8562C>T (p.Arg2854=)

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.8562C>T (p.Arg2854=)
  • NC_000011.10:g.108345886C>T
  • NG_009830.1:g.128055C>T
  • NG_054724.1:g.128947G>A
  • NM_000051.3:c.8562C>T
  • NM_001330368.2:c.641-36815G>A
  • NM_001351110.2:c.695-10594G>A
  • NM_001351834.2:c.8562C>T
  • NP_000042.3:p.Arg2854=
  • NP_001338763.1:p.Arg2854=
  • LRG_135t1:c.8562C>T
  • LRG_135:g.128055C>T
  • LRG_135p1:p.Arg2854=
  • NC_000011.9:g.108216613C>T
dbSNP: rs878853550
NCBI 1000 Genomes Browser:
Molecular consequence:
  • NM_001330368.2:c.641-36815G>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001351110.2:c.695-10594G>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000051.3:c.8562C>T - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001351834.2:c.8562C>T - synonymous variant - [Sequence Ontology: SO:0001819]


MedGen: CN169374

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
SCV000527586GeneDxcriteria provided, single submitter
Likely benign
(Oct 3, 2017)
germlineclinical testing

Citation Link,

SCV000918534Integrated Genetics/Laboratory Corporation of Americacriteria provided, single submitter
Uncertain significance
(Mar 30, 2018)
germlineclinical testing

Citation Link

Summary from all submissions

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

Details of each submission

From GeneDx, SCV000527586.4

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


This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.

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

From Integrated Genetics/Laboratory Corporation of America, SCV000918534.1

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


Variant summary: ATM c.8562C>T alters a non-conserved nucleotide resulting in a synonymous change. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 4.1e-06 in 245856 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.8562C>T in individuals affected with Ataxia-Telangiectasia and no experimental evidence demonstrating its impact on protein function have been reported. Multiple ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cite the variant as "likely benign." Based on the evidence outlined above, the variant was classified as VUS-possibly benign.

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

Last Updated: Oct 11, 2019

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