NM_000051.4(ATM):c.1931C>A (p.Ser644Ter) AND Ataxia-telangiectasia syndrome

Clinical significance:Pathogenic/Likely pathogenic (Last evaluated: Jan 29, 2020)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
2 submissions [Details]
Record status:

Allele description [Variation Report for NM_000051.4(ATM):c.1931C>A (p.Ser644Ter)]

NM_000051.4(ATM):c.1931C>A (p.Ser644Ter)

ATM:ATM serine/threonine kinase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Genomic location:
Preferred name:
NM_000051.4(ATM):c.1931C>A (p.Ser644Ter)
  • NC_000011.10:g.108253846C>A
  • NG_009830.1:g.36015C>A
  • NM_000051.4:c.1931C>AMANE SELECT
  • NM_001351834.2:c.1931C>A
  • NP_000042.3:p.Ser644Ter
  • NP_000042.3:p.Ser644Ter
  • NP_001338763.1:p.Ser644Ter
  • LRG_135t1:c.1931C>A
  • LRG_135:g.36015C>A
  • LRG_135p1:p.Ser644Ter
  • NC_000011.9:g.108124573C>A
  • NM_000051.3:c.1931C>A
Protein change:
dbSNP: rs768362387
NCBI 1000 Genomes Browser:
Molecular consequence:
  • NM_000051.4:c.1931C>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001351834.2:c.1931C>A - nonsense - [Sequence Ontology: SO:0001587]


Ataxia-telangiectasia syndrome (AT)
Louis-Bar syndrome; Cerebello-oculocutaneous telangiectasia; Immunodeficiency with ataxia telangiectasia; See all synonyms [MedGen]
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)
SCV000678107Counsylcriteria provided, single submitter
Likely pathogenic
(Jun 14, 2017)
unknownclinical testing

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

Citation Link,

SCV000825216Invitaecriteria provided, single submitter
(Jan 29, 2020)
germlineclinical testing

PubMed (7)
[See all records that cite these PMIDs]

Summary from all submissions

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



Loss-of-function variants in ATM confer risk of gastric cancer.

Helgason H, Rafnar T, Olafsdottir HS, Jonasson JG, Sigurdsson A, Stacey SN, Jonasdottir A, Tryggvadottir L, Alexiusdottir K, Haraldsson A, le Roux L, Gudmundsson J, Johannsdottir H, Oddsson A, Gylfason A, Magnusson OT, Masson G, Jonsson T, Skuladottir H, Gudbjartsson DF, Thorsteinsdottir U, Sulem P, et al.

Nat Genet. 2015 Aug;47(8):906-10. doi: 10.1038/ng.3342. Epub 2015 Jun 22.

PubMed [citation]

Exome sequencing identifies nonsegregating nonsense ATM and PALB2 variants in familial pancreatic cancer.

Grant RC, Al-Sukhni W, Borgida AE, Holter S, Kanji ZS, McPherson T, Whelan E, Serra S, Trinh QM, Peltekova V, Stein LD, McPherson JD, Gallinger S.

Hum Genomics. 2013 Apr 5;7:11. doi: 10.1186/1479-7364-7-11.

PubMed [citation]
See all PubMed Citations (7)

Details of each submission

From Counsyl, SCV000678107.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

From Invitae, SCV000825216.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (7)


This sequence change creates a premature translational stop signal (p.Ser644*) in the ATM gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals affected with gastric cancer (PMID: 26098866) and pancreatic cancer (PMID: 23561644, 25479140). Additionally this variant has been reported in combination with another ATM variant in an individual affected with ataxia telangiectasia (PMID: 10817650). ClinVar contains an entry for this variant (Variation ID: 233607). Loss-of-function variants in ATM are known to be pathogenic (PMID: 23807571, 25614872). For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: Dec 4, 2021

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