NM_000051.4(ATM):c.5763-1050A>G AND not provided

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Jul 1, 2024
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:: RCV000724150.31

Allele description [Variation Report for NM_000051.4(ATM):c.5763-1050A>G]

NM_000051.4(ATM):c.5763-1050A>G

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.5763-1050A>G

Other names:

5762ins137

HGVS:

NC_000011.10:g.108309110A>G
NG_009830.1:g.91279A>G
NG_054724.1:g.165723T>C
NM_000051.4:c.5763-1050A>GMANE SELECT
NM_001330368.2:c.641-39T>C
NM_001351110.2:c.*39-39T>C
NM_001351834.2:c.5763-1050A>G
LRG_135t1:c.5762_5763insNG_009830.1:g.91138_91274
LRG_135:g.91279A>G
NC_000011.9:g.108179837A>G
NM_000051.3:c.5762_5763insNG_009830.1:g.91138_91274
c.5762G>Ains137

Note:

The single A>G nucleotide change in intron 38 results in the insertion of 137-nt from intron 38 into the transcript between exons 38 and exon 39.

Links:

OMIM: 607585.0004; dbSNP: rs774925473

NCBI 1000 Genomes Browser:

rs774925473

Molecular consequence:

NM_000051.4:c.5763-1050A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001330368.2:c.641-39T>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001351110.2:c.*39-39T>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001351834.2:c.5763-1050A>G - intron variant - [Sequence Ontology: SO:0001627]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000700719	Eurofins Ntd Llc (ga)	criteria provided, single submitter (EGL Classification Definitions 2015)	Pathogenic (Dec 12, 2016)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 15174027, 8755918, 9463314 Citation Link,
SCV001875224	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Nov 1, 2022)	germline	clinical testing	Citation Link,
SCV001961310	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Pathogenic (Jul 1, 2024)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000700719

Eurofins Ntd Llc (ga)

criteria provided, single submitter

(EGL Classification Definitions 2015)

Pathogenic
(Dec 12, 2016)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Citation Link,

SCV001875224

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Nov 1, 2022)

germline

clinical testing

Citation Link,

SCV001961310

CeGaT Center for Human Genetics Tuebingen

criteria provided, single submitter

(CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)

Pathogenic
(Jul 1, 2024)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	4	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Adult-onset ataxia telangiectasia due to ATM 5762ins137 mutation homozygosity.

Sutton IJ, Last JI, Ritchie SJ, Harrington HJ, Byrd PJ, Taylor AM.

Ann Neurol. 2004 Jun;55(6):891-5.

PubMed [citation]

PMID:: 15174027

Mutations associated with variant phenotypes in ataxia-telangiectasia.

McConville CM, Stankovic T, Byrd PJ, McGuire GM, Yao QY, Lennox GG, Taylor MR.

Am J Hum Genet. 1996 Aug;59(2):320-30.

PubMed [citation]

PMID:: 8755918
PMCID:: PMC1914715

See all PubMed Citations (3)

Details of each submission

From Eurofins Ntd Llc (ga), SCV000700719.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (3)

#	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		1	not provided	not provided	not provided

From GeneDx, SCV001875224.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

Non-canonical splice site variant demonstrated to result in two transcripts, one with a 137 nucleotide insertion which results in a frameshift, as well as some normal transcript (McConville et al., 1996; Teraoka et al., 1999); Published functional studies demonstrate a damaging effect: cells from individuals carrying this variant have been shown to have reduced ATM protein levels and ATM kinase activity compared to wildtype (Izatt et al., 1999; Stewart et al., 2001; Sutton et al., 2004; Reiman et al., 2011; Taylor et al., 2015); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis suggests this variant may impact gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; This variant is associated with the following publications: (PMID: 9463314, 23143971, 19823873, 17586848, 25040471, 21459046, 32623769, 19535770, 11382771, 15174027, 20301790, 8755918, 10234507, 10330348, 28008555, 15928302, 12082606, 30549301, 26896183, 32255556, 21792198)

#	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 CeGaT Center for Human Genetics Tuebingen, SCV001961310.18

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	4	not provided	not provided	clinical testing	not provided

Description

ATM: PM3:Very Strong, PM2, PS3:Supporting

#	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		4	not provided	not provided	not provided

Last Updated: Oct 26, 2024

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