NM_000051.4(ATM):c.7570G>C (p.Ala2524Pro) AND Ataxia-telangiectasia syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 16, 2024
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:: RCV000550379.16

Allele description [Variation Report for NM_000051.4(ATM):c.7570G>C (p.Ala2524Pro)]

NM_000051.4(ATM):c.7570G>C (p.Ala2524Pro)

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.7570G>C (p.Ala2524Pro)

HGVS:

NC_000011.10:g.108331498G>C
NG_009830.1:g.113667G>C
NG_054724.1:g.143335C>G
NM_000051.4:c.7570G>CMANE SELECT
NM_001330368.2:c.641-22427C>G
NM_001351110.2:c.*38+3722C>G
NM_001351834.2:c.7570G>C
NM_152587.2:c.*1339C>G
NP_000042.3:p.Ala2524Pro
NP_000042.3:p.Ala2524Pro
NP_001338763.1:p.Ala2524Pro
LRG_135t1:c.7570G>C
LRG_135:g.113667G>C
LRG_135p1:p.Ala2524Pro
NC_000011.9:g.108202225G>C
NM_000051.3:c.7570G>C
NR_147053.3:n.2442C>G
p.A2524P

Protein change:

A2524P

Links:

dbSNP: rs769142993

NCBI 1000 Genomes Browser:

rs769142993

Molecular consequence:

NM_001330368.2:c.641-22427C>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001351110.2:c.*38+3722C>G - intron variant - [Sequence Ontology: SO:0001627]
NM_000051.4:c.7570G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001351834.2:c.7570G>C - missense variant - [Sequence Ontology: SO:0001583]
NR_147053.3:n.2442C>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]

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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000622760	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 16, 2024)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 10980530, 11897822, 16622469, 17166884, 22071889, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000622760

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 16, 2024)

germline

clinical testing

PubMed (6)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Characterization of ATM mutations in 41 Nordic families with ataxia telangiectasia.

Laake K, Jansen L, Hahnemann JM, Brondum-Nielsen K, Lönnqvist T, Kääriäinen H, Sankila R, Lähdesmäki A, Hammarström L, Yuen J, Tretli S, Heiberg A, Olsen JH, Tucker M, Kleinerman R, Børresen-Dale AL.

Hum Mutat. 2000 Sep;16(3):232-46.

PubMed [citation]

PMID:: 10980530

ATM mutations in Finnish breast cancer patients.

Allinen M, Launonen V, Laake K, Jansen L, Huusko P, Kääriäinen H, Børresen-Dale AL, Winqvist R.

J Med Genet. 2002 Mar;39(3):192-6. No abstract available.

PubMed [citation]

PMID:: 11897822
PMCID:: PMC1735070

See all PubMed Citations (6)

Details of each submission

From Invitae, SCV000622760.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

This sequence change replaces alanine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 2524 of the ATM protein (p.Ala2524Pro). This variant is present in population databases (rs769142993, gnomAD 0.03%). This missense change has been observed in individual(s) with ataxia-telangiectasia and/or ATM-related cancers (PMID: 10980530, 11897822, 16622469). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 187613). 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 disruptive. Experimental studies have shown that this missense change affects ATM function (PMID: 17166884, 22071889). For these reasons, this variant has been classified as Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Apr 15, 2024

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