NM_000051.4(ATM):c.1931C>A (p.Ser644Ter) AND Ataxia-telangiectasia syndrome

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: Apr 25, 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:: RCV000576759.12

Allele description [Variation Report for NM_000051.4(ATM):c.1931C>A (p.Ser644Ter)]

NM_000051.4(ATM):c.1931C>A (p.Ser644Ter)

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.1931C>A (p.Ser644Ter)

HGVS:

NC_000011.10:g.108253846C>A
NG_009830.1:g.36015C>A
NM_000051.4:c.1931C>AMANE SELECT
NM_001351834.2:c.1931C>A
NP_000042.3:p.Ser644Ter
NP_000042.3:p.Ser644Ter
NP_001338763.1:p.Ser644Ter
LRG_135t1:c.1931C>A
LRG_135:g.36015C>A
LRG_135p1:p.Ser644Ter
NC_000011.9:g.108124573C>A
NM_000051.3:c.1931C>A

Protein change:

S644*

Links:

dbSNP: rs768362387

NCBI 1000 Genomes Browser:

rs768362387

Molecular consequence:

NM_000051.4:c.1931C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001351834.2:c.1931C>A - nonsense - [Sequence Ontology: SO:0001587]

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
SCV000678107	Counsyl	criteria provided, single submitter (Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015))	Likely pathogenic (Jun 14, 2017)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link,
SCV000825216	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Apr 25, 2023)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 10817650, 23561644, 25479140, 26098866, 23807571, 25614872, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000678107

Counsyl

criteria provided, single submitter

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

Likely pathogenic
(Jun 14, 2017)

unknown

clinical testing

PubMed (1)
[See all records that cite this PMID]

Citation Link,

SCV000825216

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Apr 25, 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	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

Mutations at the ataxia-telangiectasia locus and clinical phenotypes of A-T patients.

Li A, Swift M.

Am J Med Genet. 2000 May 29;92(3):170-7.

PubMed [citation]

PMID:: 10817650

Exome sequencing identifies nonsegregating nonsense ATM and PALB2 variants in familial pancreatic cancer.

Grant RC, Al-Sukhni W, Borgida AE, Holter S, Kanji ZS, McPherson T, Whelan E, Serra S, Trinh QM, Peltekova V, Stein LD, McPherson JD, Gallinger S.

Hum Genomics. 2013 Apr 5;7:11. doi: 10.1186/1479-7364-7-11.

PubMed [citation]

PMID:: 23561644
PMCID:: PMC3639869

See all PubMed Citations (7)

Details of each submission

From Counsyl, SCV000678107.1

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

#	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 Labcorp Genetics (formerly Invitae), Labcorp, SCV000825216.7

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

Description

For these reasons, this variant has been classified as Pathogenic. RNA analysis performed to evaluate the impact of this premature translational stop signal on mRNA splicing indicates it does not significantly alter splicing (Invitae). ClinVar contains an entry for this variant (Variation ID: 233607). This premature translational stop signal has been observed in individual(s) with gastric cancer, pancreatic cancer, and ataxia telangiectasia (PMID: 10817650, 23561644, 25479140, 26098866). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ser644*) in the ATM gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ATM are known to be pathogenic (PMID: 23807571, 25614872).

#	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 29, 2024

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