NM_000051.4(ATM):c.986G>A (p.Arg329Lys) AND Ataxia-telangiectasia syndrome

Germline classification:: Uncertain significance (3 submissions)
Last evaluated:: Jun 11, 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:: RCV000227018.9

Allele description [Variation Report for NM_000051.4(ATM):c.986G>A (p.Arg329Lys)]

NM_000051.4(ATM):c.986G>A (p.Arg329Lys)

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.986G>A (p.Arg329Lys)

HGVS:

NC_000011.10:g.108247048G>A
NG_009830.1:g.29217G>A
NM_000051.4:c.986G>AMANE SELECT
NM_001351834.2:c.986G>A
NP_000042.3:p.Arg329Lys
NP_000042.3:p.Arg329Lys
NP_001338763.1:p.Arg329Lys
LRG_135t1:c.986G>A
LRG_135:g.29217G>A
LRG_135p1:p.Arg329Lys
NC_000011.9:g.108117775G>A
NM_000051.3:c.986G>A

Protein change:

R329K

Links:

dbSNP: rs776938735

NCBI 1000 Genomes Browser:

rs776938735

Molecular consequence:

NM_000051.4:c.986G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001351834.2:c.986G>A - 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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Tssr19068 AND (alive[prop]) (0)
Gene
HAD superfamily (subfamily IF) hydrolase, YfhB [Salmonella enterica subsp. enter...
HAD superfamily (subfamily IF) hydrolase, YfhB [Salmonella enterica subsp. enterica serovar Heidelberg str. SL476]
gi|194406090|gnl|tigr|SeHA_C2835|gb 6309.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000283107	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 9, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001456875	Natera, Inc.	no assertion criteria provided	Uncertain significance (Sep 16, 2020)	germline	clinical testing
SCV005050147	Department of Human Genetics, Hannover Medical School	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Jun 11, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000283107

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 9, 2024)

germline

clinical testing

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

SCV001456875

Natera, Inc.

no assertion criteria provided

Uncertain significance
(Sep 16, 2020)

germline

clinical testing

SCV005050147

Department of Human Genetics, Hannover Medical School

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Jun 11, 2024)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	no	not provided	not provided	not provided	not provided	not provided	clinical testing
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

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000283107.7

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

Description

This sequence change replaces arginine, which is basic and polar, with lysine, which is basic and polar, at codon 329 of the ATM protein (p.Arg329Lys). This variant is present in population databases (rs776938735, gnomAD 0.05%). This variant has not been reported in the literature in individuals affected with ATM-related conditions. ClinVar contains an entry for this variant (Variation ID: 236798). 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 disruptive. 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., SCV001456875.1

#	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

From Department of Human Genetics, Hannover Medical School, SCV005050147.1

#	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	germline	no	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Oct 13, 2024

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