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NM_000051.4(ATM):c.1440A>T (p.Leu480Phe) AND Ataxia-telangiectasia syndrome

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Nov 9, 2016
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV000461934.7

Allele description [Variation Report for NM_000051.4(ATM):c.1440A>T (p.Leu480Phe)]

NM_000051.4(ATM):c.1440A>T (p.Leu480Phe)

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.1440A>T (p.Leu480Phe)
HGVS:
  • NC_000011.10:g.108250905A>T
  • NG_009830.1:g.33074A>T
  • NM_000051.4:c.1440A>TMANE SELECT
  • NM_001351834.2:c.1440A>T
  • NP_000042.3:p.Leu480Phe
  • NP_000042.3:p.Leu480Phe
  • NP_001338763.1:p.Leu480Phe
  • LRG_135t1:c.1440A>T
  • LRG_135:g.33074A>T
  • LRG_135p1:p.Leu480Phe
  • NC_000011.9:g.108121632A>T
  • NM_000051.3:c.1440A>T
Protein change:
L480F
Links:
dbSNP: rs370240037
NCBI 1000 Genomes Browser:
rs370240037
Molecular consequence:
  • NM_000051.4:c.1440A>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001351834.2:c.1440A>T - missense variant - [Sequence Ontology: SO:0001583]

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

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000546877Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Nov 9, 2016) 		germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

Sequence variant discovery in DNA repair genes from radiosensitive and radiotolerant prostate brachytherapy patients.

Pugh TJ, Keyes M, Barclay L, Delaney A, Krzywinski M, Thomas D, Novik K, Yang C, Agranovich A, McKenzie M, Morris WJ, Olive PL, Marra MA, Moore RA.

Clin Cancer Res. 2009 Aug 1;15(15):5008-16. doi: 10.1158/1078-0432.CCR-08-3357. Epub 2009 Jul 28.

PubMed [citation]
PMID:
19638463

Integrated analysis of germline and somatic variants in ovarian cancer.

Kanchi KL, Johnson KJ, Lu C, McLellan MD, Leiserson MD, Wendl MC, Zhang Q, Koboldt DC, Xie M, Kandoth C, McMichael JF, Wyczalkowski MA, Larson DE, Schmidt HK, Miller CA, Fulton RS, Spellman PT, Mardis ER, Druley TE, Graubert TA, Goodfellow PJ, Raphael BJ, et al.

Nat Commun. 2014;5:3156. doi: 10.1038/ncomms4156.

PubMed [citation]
PMID:
24448499
PMCID:
PMC4025965
See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000546877.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a ATM-related disease. This sequence change replaces leucine with phenylalanine at codon 480 of the ATM protein (p.Leu480Phe). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and phenylalanine. A different variant (c.1440A>C), giving rise to the same protein effect (p.Leu480Phe) has been reported in an individual affected with prostate cancer (PMID: 19638463), as well as in individuals with ovarian cancer (PMID: 24448499, 26689913). In summary, this variant is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance.

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

Last Updated: Sep 29, 2024