NM_000051.3(ATM):c.640delT (p.Ser214Profs) AND Ataxia-telangiectasia syndrome

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: Dec 18, 2017
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:: RCV000169254.1

Allele description

NM_000051.3(ATM):c.640delT (p.Ser214Profs)

Gene:

ATM:ATM serine/threonine kinase [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

11q22.3

Genomic location:

Preferred name:

NM_000051.3(ATM):c.640delT (p.Ser214Profs)

HGVS:

NC_000011.10:g.108244096delT
NG_009830.1:g.26265delT
NM_000051.3:c.640delT
NP_000042.3:p.Ser214Profs
LRG_135t1:c.640delT
LRG_135:g.26265delT
LRG_135p1:p.Ser214Profs
NC_000011.9:g.108114823delT

Links:

dbSNP: rs786204543

NCBI 1000 Genomes Browser:

rs786204543

Molecular consequence:

NM_000051.3:c.640delT - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Ataxia-telangiectasia syndrome (AT)
Synonyms:: Louis-Bar syndrome; Cerebello-oculocutaneous telangiectasia; Immunodeficiency with ataxia telangiectasia; See all synonyms [MedGen]
Identifiers:: MedGen: C0004135; Orphanet: 100; OMIM: 208900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000220538	Counsyl	criteria provided, single submitter (Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015))	Likely pathogenic (Jul 23, 2014)	unknown	literature only	PubMed (4) [See all records that cite these PMIDs] 8789452, 12815592, 21965147, 15039971 Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015), Citation Link,
SCV000748987	Invitae	criteria provided, single submitter (Nykamp K et al. (Genet Med 2017))	Pathogenic (Dec 18, 2017)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 21965147, 26681312, 12815592, 8789452, 21445571, 15039971, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000220538

Counsyl

criteria provided, single submitter

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

Likely pathogenic
(Jul 23, 2014)

unknown

literature only

PubMed (4)
[See all records that cite these PMIDs]

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

Citation Link,

SCV000748987

Invitae

criteria provided, single submitter

(Nykamp K et al. (Genet Med 2017))

Pathogenic
(Dec 18, 2017)

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	unknown	unknown	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

Citations

PubMed

New mutations in the ATM gene and clinical data of 25 AT patients.

Demuth I, Dutrannoy V, Marques W Jr, Neitzel H, Schindler D, Dimova PS, Chrzanowska KH, Bojinova V, Gregorek H, Graul-Neumann LM, von Moers A, Schulze I, Nicke M, Bora E, Cankaya T, Oláh É, Kiss C, Bessenyei B, Szakszon K, Gruber-Sedlmayr U, Kroisel PM, Sodia S, et al.

Neurogenetics. 2011 Nov;12(4):273-82. doi: 10.1007/s10048-011-0299-0. Epub 2011 Oct 2.

PubMed [citation]

PMID:: 21965147

Pathogenic and likely pathogenic variant prevalence among the first 10,000 patients referred for next-generation cancer panel testing.

Susswein LR, Marshall ML, Nusbaum R, Vogel Postula KJ, Weissman SM, Yackowski L, Vaccari EM, Bissonnette J, Booker JK, Cremona ML, Gibellini F, Murphy PD, Pineda-Alvarez DE, Pollevick GD, Xu Z, Richard G, Bale S, Klein RT, Hruska KS, Chung WK.

Genet Med. 2016 Aug;18(8):823-32. doi: 10.1038/gim.2015.166. Epub 2015 Dec 17. Erratum in: Genet Med. 2016 May;18(5):531-2.

PubMed [citation]

PMID:: 26681312
PMCID:: PMC4985612

See all PubMed Citations (7)

Details of each submission

From Counsyl, SCV000220538.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (4)

#	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, SCV000748987.1

#	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 creates a premature translational stop signal (p.Ser214Profs*16) in the ATM gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been reported in the homozygous and compound heterozygous states in several individuals affected with ataxia-telangiectasia (PMID: 8789452, 21965147, 12815592, 15039971). It has also been observed in the heterozygous state in individuals affected with breast cancer or referred for cancer panel testing (PMID: 21445571, 26681312). ClinVar contains an entry for this variant (Variation ID: 188895). Loss-of-function variants in ATM are known to be pathogenic (PMID: 23807571, 25614872). 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: Jul 21, 2018

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