U.S. flag

An official website of the United States government

NM_000051.4(ATM):c.7739G>A (p.Arg2580Lys) AND Ataxia-telangiectasia syndrome

Germline classification:
Pathogenic (2 submissions)
Last evaluated:
Dec 15, 2023
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:
RCV001218403.17

Allele description [Variation Report for NM_000051.4(ATM):c.7739G>A (p.Arg2580Lys)]

NM_000051.4(ATM):c.7739G>A (p.Arg2580Lys)

Genes:
ATM:ATM serine/threonine kinase [Gene - OMIM - HGNC]
C11orf65:chromosome 11 open reading frame 65 [Gene - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
11q22.3
Genomic location:
Preferred name:
NM_000051.4(ATM):c.7739G>A (p.Arg2580Lys)
HGVS:
  • NC_000011.10:g.108331988G>A
  • NG_009830.1:g.114157G>A
  • NG_054724.1:g.142845C>T
  • NM_000051.4:c.7739G>AMANE SELECT
  • NM_001330368.2:c.641-22917C>T
  • NM_001351110.2:c.*38+3232C>T
  • NM_001351834.2:c.7739G>A
  • NP_000042.3:p.Arg2580Lys
  • NP_000042.3:p.Arg2580Lys
  • NP_001338763.1:p.Arg2580Lys
  • LRG_135t1:c.7739G>A
  • LRG_135:g.114157G>A
  • LRG_135p1:p.Arg2580Lys
  • NC_000011.9:g.108202715G>A
  • NM_000051.3:c.7739G>A
Protein change:
R2580K
Links:
dbSNP: rs761790685
NCBI 1000 Genomes Browser:
rs761790685
Molecular consequence:
  • NM_001330368.2:c.641-22917C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001351110.2:c.*38+3232C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000051.4:c.7739G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001351834.2:c.7739G>A - 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

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)
OriginMethodCitations
SCV001390285Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Pathogenic
(Dec 15, 2023)
germlineclinical testing

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

SCV002083589Natera, Inc.
no assertion criteria provided
Uncertain significance
(Mar 7, 2020)
germlineclinical testing

Summary from all submissions

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

Citations

PubMed

A single ataxia telangiectasia gene with a product similar to PI-3 kinase.

Savitsky K, Bar-Shira A, Gilad S, Rotman G, Ziv Y, Vanagaite L, Tagle DA, Smith S, Uziel T, Sfez S, Ashkenazi M, Pecker I, Frydman M, Harnik R, Patanjali SR, Simmons A, Clines GA, Sartiel A, Gatti RA, Chessa L, Sanal O, Lavin MF, et al.

Science. 1995 Jun 23;268(5218):1749-53.

PubMed [citation]
PMID:
7792600

ATM mutations in cancer families.

Vorechovský I, Luo L, Lindblom A, Negrini M, Webster AD, Croce CM, Hammarström L.

Cancer Res. 1996 Sep 15;56(18):4130-3.

PubMed [citation]
PMID:
8797579
See all PubMed Citations (7)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001390285.5

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

Description

This sequence change replaces arginine, which is basic and polar, with lysine, which is basic and polar, at codon 2580 of the ATM protein (p.Arg2580Lys). RNA analysis indicates that this missense change induces altered splicing and likely results in a shortened protein product. This variant is present in population databases (rs761790685, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with ATM-related conditions. ClinVar contains an entry for this variant (Variation ID: 478937). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. Studies have shown that this missense change results in skipping of exon 52, but is expected to preserve the integrity of the reading-frame (Invitae). This variant disrupts a region of the ATM protein in which other variant(s) (p.Arg2547_Ser2549del) have been determined to be pathogenic (PMID: 7792600, 8797579, 11382771, 12552559, 21787400, 22649200). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.

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

From Natera, Inc., SCV002083589.1

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

Last Updated: Feb 8, 2025