NM_000051.4(ATM):c.3372C>G (p.Tyr1124Ter) AND Hereditary cancer-predisposing syndrome

Clinical significance:Pathogenic (Last evaluated: Aug 20, 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.3372C>G (p.Tyr1124Ter)]

NM_000051.4(ATM):c.3372C>G (p.Tyr1124Ter)

ATM:ATM serine/threonine kinase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Genomic location:
Preferred name:
NM_000051.4(ATM):c.3372C>G (p.Tyr1124Ter)
Other names:
  • NC_000011.10:g.108279578C>G
  • NG_009830.1:g.61747C>G
  • NM_000051.4:c.3372C>GMANE SELECT
  • NM_001351834.2:c.3372C>G
  • NP_000042.3:p.Tyr1124Ter
  • NP_000042.3:p.Tyr1124Ter
  • NP_001338763.1:p.Tyr1124Ter
  • LRG_135t1:c.3372C>G
  • LRG_135:g.61747C>G
  • LRG_135p1:p.Tyr1124Ter
  • NC_000011.9:g.108150305C>G
  • NM_000051.3:c.3372C>G
  • p.Tyr1124Stop
  • p.Y1124*
Protein change:
dbSNP: rs587779833
NCBI 1000 Genomes Browser:
Molecular consequence:
  • NM_000051.4:c.3372C>G - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001351834.2:c.3372C>G - nonsense - [Sequence Ontology: SO:0001587]


Hereditary cancer-predisposing syndrome
Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
MONDO: MONDO:0015356; MedGen: C0027672

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
SCV000186133Ambry Geneticscriteria provided, single submitter
(Apr 24, 2018)
germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Citation Link,

SCV000911665Color Health, Inccriteria provided, single submitter
(Aug 20, 2020)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown1not providednot provided1not providedclinical testing



Splicing defects in the ataxia-telangiectasia gene, ATM: underlying mutations and consequences.

Teraoka SN, Telatar M, Becker-Catania S, Liang T, Oneng├╝t S, Tolun A, Chessa L, Sanal O, Bernatowska E, Gatti RA, Concannon P.

Am J Hum Genet. 1999 Jun;64(6):1617-31.

PubMed [citation]

Mutations at the ataxia-telangiectasia locus and clinical phenotypes of A-T patients.

Li A, Swift M.

Am J Med Genet. 2000 May 29;92(3):170-7.

PubMed [citation]
See all PubMed Citations (4)

Details of each submission

From Ambry Genetics, SCV000186133.6

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (3)


The p.Y1124* pathogenic mutation (also known as c.3372C>G), located in coding exon 22 of the ATM gene, results from a C to G substitution at nucleotide position 3372. This changes the amino acid from a tyrosine to a stop codon within coding exon 22. This mutation has been reported as both heterozygous and homozygous in ataxia-telangiectasia (A-T) patients to date (Teraoka SN et al. Am. J. Hum. Genet. 1999 Jun;64:1617-31; Li A and Swift M. Am. J. Med. Genet. 2000 May;92:170-7). This alteration has also been identified in an individual with breast cancer and pulmonary carcinoid (Susswein LR et al. Genet. Med. 2016 Aug;18:823-32). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.

OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknown1not providednot provided1not providednot providednot provided

From Color Health, Inc, SCV000911665.3

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


This variant changes 1 nucleotide in exon 23 of the ATM gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in the homozygous and heterozygous state in individuals affected with ataxia telangiectasia (PMID: 10330348, 10817650). This variant has also been reported in an individual affected with breast and lung cancer (PMID: 26681312). This variant has been identified in 1/250920 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Loss of ATM function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.

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

Last Updated: Dec 4, 2021

Support Center