NM_000051.4(ATM):c.1814A>G (p.His605Arg) AND Ataxia-telangiectasia syndrome

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Jan 29, 2024
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV000628205.13

Allele description [Variation Report for NM_000051.4(ATM):c.1814A>G (p.His605Arg)]

NM_000051.4(ATM):c.1814A>G (p.His605Arg)

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.1814A>G (p.His605Arg)

HGVS:

NC_000011.10:g.108252828A>G
NG_009830.1:g.34997A>G
NM_000051.4:c.1814A>GMANE SELECT
NM_001351834.2:c.1814A>G
NP_000042.3:p.His605Arg
NP_000042.3:p.His605Arg
NP_001338763.1:p.His605Arg
LRG_135t1:c.1814A>G
LRG_135:g.34997A>G
LRG_135p1:p.His605Arg
NC_000011.9:g.108123555A>G
NM_000051.3:c.1814A>G

Protein change:

H605R

Links:

dbSNP: rs771877351

NCBI 1000 Genomes Browser:

rs771877351

Molecular consequence:

NM_000051.4:c.1814A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001351834.2:c.1814A>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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000749099	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 29, 2024)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 16914028, 20305132, 28492532
SCV002083901	Natera, Inc.	no assertion criteria provided	Uncertain significance (Sep 28, 2021)	germline	clinical testing

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000749099

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 29, 2024)

germline

clinical testing

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

SCV002083901

Natera, Inc.

no assertion criteria provided

Uncertain significance
(Sep 28, 2021)

germline

clinical testing

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

Citations

PubMed

ATM variants and cancer risk in breast cancer patients from Southern Finland.

Tommiska J, Jansen L, Kilpivaara O, Edvardsen H, Kristensen V, Tamminen A, Aittomäki K, Blomqvist C, Børresen-Dale AL, Nevanlinna H.

BMC Cancer. 2006 Aug 16;6:209.

PubMed [citation]

PMID:: 16914028
PMCID:: PMC1592307

Radiation exposure, the ATM Gene, and contralateral breast cancer in the women's environmental cancer and radiation epidemiology study.

Bernstein JL, Haile RW, Stovall M, Boice JD Jr, Shore RE, Langholz B, Thomas DC, Bernstein L, Lynch CF, Olsen JH, Malone KE, Mellemkjaer L, Borresen-Dale AL, Rosenstein BS, Teraoka SN, Diep AT, Smith SA, Capanu M, Reiner AS, Liang X, Gatti RA, Concannon P; et al.

J Natl Cancer Inst. 2010 Apr 7;102(7):475-83. doi: 10.1093/jnci/djq055. Epub 2010 Mar 19.

PubMed [citation]

PMID:: 20305132
PMCID:: PMC2902825

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000749099.7

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

Description

This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 605 of the ATM protein (p.His605Arg). This variant is present in population databases (rs771877351, gnomAD 0.01%). This missense change has been observed in individual(s) with breast cancer (PMID: 16914028, 20305132). ClinVar contains an entry for this variant (Variation ID: 246258). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant¬†is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain 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

From Natera, Inc., SCV002083901.1

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

#	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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