NM_000051.4(ATM):c.3078-1G>A AND Ataxia-telangiectasia syndrome

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: Jan 25, 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:: RCV000410565.9

Allele description [Variation Report for NM_000051.4(ATM):c.3078-1G>A]

NM_000051.4(ATM):c.3078-1G>A

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.3078-1G>A

HGVS:

NC_000011.10:g.108272531G>A
NG_009830.1:g.54700G>A
NM_000051.4:c.3078-1G>AMANE SELECT
NM_001351834.2:c.3078-1G>A
LRG_135t1:c.3078-1G>A
LRG_135:g.54700G>A
NC_000011.9:g.108143258G>A
NM_000051.3:c.3078-1G>A

Links:

dbSNP: rs750663117

NCBI 1000 Genomes Browser:

rs750663117

Molecular consequence:

NM_000051.4:c.3078-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001351834.2:c.3078-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]

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
SCV000486113	Counsyl	criteria provided, single submitter (Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015))	Likely pathogenic (Mar 31, 2016)	unknown	clinical testing	PubMed (2) [See all records that cite these PMIDs] 25525159, 10234507 mdi-5618_320494_Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015).pdf, Citation Link,
SCV000622387	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 25, 2024)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 10234507, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000486113

Counsyl

criteria provided, single submitter

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

Likely pathogenic
(Mar 31, 2016)

unknown

clinical testing

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

mdi-5618_320494_Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015).pdf,

Citation Link,

SCV000622387

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 25, 2024)

germline

clinical testing

PubMed (2)
[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
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

RNA splicing. The human splicing code reveals new insights into the genetic determinants of disease.

Xiong HY, Alipanahi B, Lee LJ, Bretschneider H, Merico D, Yuen RK, Hua Y, Gueroussov S, Najafabadi HS, Hughes TR, Morris Q, Barash Y, Krainer AR, Jojic N, Scherer SW, Blencowe BJ, Frey BJ.

Science. 2015 Jan 9;347(6218):1254806. doi: 10.1126/science.1254806. Epub 2014 Dec 18.

PubMed [citation]

PMID:: 25525159
PMCID:: PMC4362528

Rapid and efficient ATM mutation detection by fluorescent chemical cleavage of mismatch: identification of four novel mutations.

Izatt L, Vessey C, Hodgson SV, Solomon E.

Eur J Hum Genet. 1999 Apr;7(3):310-20.

PubMed [citation]

PMID:: 10234507

See all PubMed Citations (3)

Details of each submission

From Counsyl, SCV000486113.2

#	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, SCV000622387.7

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

Description

This sequence change affects an acceptor splice site in intron 20 of the ATM gene. RNA analysis indicates that disruption of this splice site induces altered splicing and may result in an absent or disrupted protein product. This variant is present in population databases (rs750663117, gnomAD 0.003%). Disruption of this splice site has been observed in individual(s) with clinical features of ataxia-telangiectasia (PMID: 10234507). 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: 231277). Studies have shown that disruption of this splice site results in skipping of exon 21 and introduces a premature termination codon (PMID: 10234507; Invitae). The resulting mRNA is expected to undergo nonsense-mediated decay. 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: Sep 16, 2024

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