NM_000051.4(ATM):c.1A>G (p.Met1Val) AND Ataxia-telangiectasia syndrome

Germline classification:: Pathogenic/Likely pathogenic (3 submissions)
Last evaluated:: Dec 8, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000258119.16

Allele description [Variation Report for NM_000051.4(ATM):c.1A>G (p.Met1Val)]

NM_000051.4(ATM):c.1A>G (p.Met1Val)

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.1A>G (p.Met1Val)

HGVS:

NC_000011.10:g.108227625A>G
NG_009830.1:g.9794A>G
NM_000051.4:c.1A>GMANE SELECT
NM_001351834.2:c.1A>G
NM_001351835.2:c.1A>G
NM_001351836.2:c.1A>G
NP_000042.3:p.Met1Val
NP_000042.3:p.Met1Val
NP_001338763.1:p.Met1Val
NP_001338764.1:p.Met1Val
NP_001338765.1:p.Met1Val
LRG_135t1:c.1A>G
LRG_135:g.9794A>G
LRG_135p1:p.Met1Val
NC_000011.9:g.108098352A>G
NM_000051.3:c.1A>G

Protein change:

M1V

Links:

dbSNP: rs730881359

NCBI 1000 Genomes Browser:

rs730881359

Molecular consequence:

NM_000051.4:c.1A>G - initiator_codon_variant - [Sequence Ontology: SO:0001582]
NM_001351834.2:c.1A>G - initiator_codon_variant - [Sequence Ontology: SO:0001582]
NM_001351835.2:c.1A>G - initiator_codon_variant - [Sequence Ontology: SO:0001582]
NM_001351836.2:c.1A>G - initiator_codon_variant - [Sequence Ontology: SO:0001582]
NM_000051.4:c.1A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001351834.2:c.1A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001351835.2:c.1A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001351836.2:c.1A>G - 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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000328265	GeneReviews	no classification provided	not provided	germline	literature only
SCV000678094	Counsyl	criteria provided, single submitter (Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015))	Likely pathogenic (Nov 29, 2016)	unknown	clinical testing	PubMed (2) [See all records that cite these PMIDs] 22146522, 21665257 Citation Link,
SCV001583011	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 8, 2023)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 9463314, 12552559, 21665257, 21792198, 22146522, 22649200, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000328265

GeneReviews

no classification provided

not provided

germline

literature only

SCV000678094

Counsyl

criteria provided, single submitter

(Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015))

Likely pathogenic
(Nov 29, 2016)

unknown

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link,

SCV001583011

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 8, 2023)

germline

clinical testing

PubMed (7)
[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	yes	not provided	not provided	not provided	not provided	not provided	literature only
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

ATM mutations and phenotypes in ataxia-telangiectasia families in the British Isles: expression of mutant ATM and the risk of leukemia, lymphoma, and breast cancer.

Stankovic T, Kidd AM, Sutcliffe A, McGuire GM, Robinson P, Weber P, Bedenham T, Bradwell AR, Easton DF, Lennox GG, Haites N, Byrd PJ, Taylor AM.

Am J Hum Genet. 1998 Feb;62(2):334-45.

PubMed [citation]

PMID:: 9463314
PMCID:: PMC1376883

Comprehensive scanning of the ATM gene with DOVAM-S.

Buzin CH, Gatti RA, Nguyen VQ, Wen CY, Mitui M, Sanal O, Chen JS, Nozari G, Mengos A, Li X, Fujimura F, Sommer SS.

Hum Mutat. 2003 Feb;21(2):123-31.

PubMed [citation]

PMID:: 12552559

See all PubMed Citations (7)

Details of each submission

From GeneReviews, SCV000328265.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	not provided

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

From Counsyl, SCV000678094.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

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

From Invitae, SCV001583011.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (7)

Description

This sequence change affects the initiator methionine of the ATM mRNA. The next in-frame methionine is located at codon 94. This variant is not present in population databases (gnomAD no frequency). Disruption of the initiator codon has been observed in individuals with ataxia-telangiectasia (PMID: 9463314, 12552559, 21665257, 21792198, 22146522, 22649200). ClinVar contains an entry for this variant (Variation ID: 181942). 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 20, 2024

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