NM_000051.4(ATM):c.5554C>T (p.Gln1852Ter) AND Ataxia-telangiectasia syndrome

Clinical significance:Pathogenic/Likely pathogenic (Last evaluated: Oct 19, 2020)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000409717.3

Allele description [Variation Report for NM_000051.4(ATM):c.5554C>T (p.Gln1852Ter)]

NM_000051.4(ATM):c.5554C>T (p.Gln1852Ter)

Gene:
ATM:ATM serine/threonine kinase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
11q22.3
Genomic location:
Preferred name:
NM_000051.4(ATM):c.5554C>T (p.Gln1852Ter)
HGVS:
  • NC_000011.10:g.108304732C>T
  • NG_009830.1:g.86901C>T
  • NM_000051.4:c.5554C>TMANE SELECT
  • NM_001351834.2:c.5554C>T
  • NP_000042.3:p.Gln1852Ter
  • NP_000042.3:p.Gln1852Ter
  • NP_001338763.1:p.Gln1852Ter
  • LRG_135t1:c.5554C>T
  • LRG_135:g.86901C>T
  • LRG_135p1:p.Gln1852Ter
  • NC_000011.9:g.108175459C>T
  • NM_000051.3:c.5554C>T
Protein change:
Q1852*
Links:
dbSNP: rs754562056
NCBI 1000 Genomes Browser:
rs754562056
Molecular consequence:
  • NM_000051.4:c.5554C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001351834.2:c.5554C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:
Ataxia-telangiectasia syndrome (AT)
Synonyms:
Louis-Bar syndrome; Cerebello-oculocutaneous telangiectasia; Immunodeficiency with ataxia telangiectasia; See all synonyms [MedGen]
Identifiers:
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)
OriginMethodCitations
SCV000485972Counsylcriteria provided, single submitter
Likely pathogenic
(Mar 10, 2016)
unknownclinical testing

mdi-5618_320494_Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015).pdf,

Citation Link,

SCV001401485Invitaecriteria provided, single submitter
Pathogenic
(Oct 19, 2020)
germlineclinical testing

PubMed (5)
[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

Citations

PubMed

Next-generation sequencing for the diagnosis of hereditary breast and ovarian cancer using genomic capture targeting multiple candidate genes.

Castéra L, Krieger S, Rousselin A, Legros A, Baumann JJ, Bruet O, Brault B, Fouillet R, Goardon N, Letac O, Baert-Desurmont S, Tinat J, Bera O, Dugast C, Berthet P, Polycarpe F, Layet V, Hardouin A, Frébourg T, Vaur D.

Eur J Hum Genet. 2014 Nov;22(11):1305-13. doi: 10.1038/ejhg.2014.16. Epub 2014 Feb 19.

PubMed [citation]
PMID:
24549055
PMCID:
PMC4200427

Rare, protein-truncating variants in ATM, CHEK2 and PALB2, but not XRCC2, are associated with increased breast cancer risks.

Decker B, Allen J, Luccarini C, Pooley KA, Shah M, Bolla MK, Wang Q, Ahmed S, Baynes C, Conroy DM, Brown J, Luben R, Ostrander EA, Pharoah PD, Dunning AM, Easton DF.

J Med Genet. 2017 Nov;54(11):732-741. doi: 10.1136/jmedgenet-2017-104588. Epub 2017 Aug 4.

PubMed [citation]
PMID:
28779002
PMCID:
PMC5740532
See all PubMed Citations (5)

Details of each submission

From Counsyl, SCV000485972.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

From Invitae, SCV001401485.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

This sequence change creates a premature translational stop signal (p.Gln1852*) in the ATM gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs754562056, ExAC 0.002%). This variant has been observed in individuals with personal or family history of breast and/or ovarian cancer (PMID: 24549055, 28779002). ClinVar contains an entry for this variant (Variation ID: 370611). Loss-of-function variants in ATM are known to be pathogenic (PMID: 23807571, 25614872). For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: Dec 4, 2021

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