NM_000051.4(ATM):c.4066A>G (p.Asn1356Asp) AND Ataxia-telangiectasia syndrome

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: Feb 1, 2024
Review status:: criteria provided, conflicting classifications

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:: RCV000122846.34

Allele description [Variation Report for NM_000051.4(ATM):c.4066A>G (p.Asn1356Asp)]

NM_000051.4(ATM):c.4066A>G (p.Asn1356Asp)

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.4066A>G (p.Asn1356Asp)

Other names:

p.N1356D:AAT>GAT

HGVS:

NC_000011.10:g.108287672A>G
NG_009830.1:g.69841A>G
NM_000051.4:c.4066A>GMANE SELECT
NM_001351834.2:c.4066A>G
NP_000042.3:p.Asn1356Asp
NP_000042.3:p.Asn1356Asp
NP_001338763.1:p.Asn1356Asp
LRG_135t1:c.4066A>G
LRG_135:g.69841A>G
LRG_135p1:p.Asn1356Asp
NC_000011.9:g.108158399A>G
NM_000051.3:c.4066A>G
p.N1356D

Protein change:

N1356D

Links:

dbSNP: rs147600485

NCBI 1000 Genomes Browser:

rs147600485

Molecular consequence:

NM_000051.4:c.4066A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001351834.2:c.4066A>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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MBTPS2 membrane bound transcription factor peptidase, site 2 [Homo sapiens]
MBTPS2 membrane bound transcription factor peptidase, site 2 [Homo sapiens]
Gene ID:51360

Gene
Gene Links for GEO Profiles (Select 116807737) (1)
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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000166104	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely benign (Feb 1, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001262666	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Uncertain significance (Apr 27, 2017)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000166104

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely benign
(Feb 1, 2024)

germline

clinical testing

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

SCV001262666

Illumina Laboratory Services, Illumina

criteria provided, single submitter

(ICSL Variant Classification Criteria 13 December 2019)

Uncertain significance
(Apr 27, 2017)

germline

clinical testing

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

Citation Link

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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

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

ATM missense mutations are frequent in patients with breast cancer.

Sommer SS, Jiang Z, Feng J, Buzin CH, Zheng J, Longmate J, Jung M, Moulds J, Dritschilo A.

Cancer Genet Cytogenet. 2003 Sep;145(2):115-20.

PubMed [citation]

PMID:: 12935922

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000166104.16

#	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	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Illumina Laboratory Services, Illumina, SCV001262666.1

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

Description

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.

#	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: Nov 10, 2024

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