NM_000051.4(ATM):c.3743A>G (p.Tyr1248Cys) AND Ataxia-telangiectasia syndrome

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Jan 9, 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:: RCV000471000.11

Allele description [Variation Report for NM_000051.4(ATM):c.3743A>G (p.Tyr1248Cys)]

NM_000051.4(ATM):c.3743A>G (p.Tyr1248Cys)

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.3743A>G (p.Tyr1248Cys)

HGVS:

NC_000011.10:g.108282876A>G
NG_009830.1:g.65045A>G
NM_000051.4:c.3743A>GMANE SELECT
NM_001351834.2:c.3743A>G
NP_000042.3:p.Tyr1248Cys
NP_000042.3:p.Tyr1248Cys
NP_001338763.1:p.Tyr1248Cys
LRG_135t1:c.3743A>G
LRG_135:g.65045A>G
LRG_135p1:p.Tyr1248Cys
NC_000011.9:g.108153603A>G
NM_000051.3:c.3743A>G

Protein change:

Y1248C

Links:

dbSNP: rs766226370

NCBI 1000 Genomes Browser:

rs766226370

Molecular consequence:

NM_000051.4:c.3743A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001351834.2:c.3743A>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

Recent activity

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Rattus norvegicus strain BN chromosome 3 CRA_213000034335816, whole genome shotg...
Rattus norvegicus strain BN chromosome 3 CRA_213000034335816, whole genome shotgun sequence
gi|70580461|gb|AAHX01025390.1||gnl| AHX|CRA_213000034335816

Nucleotide
Mus musculus CRL-1722 L5178Y-R cDNA, RIKEN full-length enriched library, clone:I...
Mus musculus CRL-1722 L5178Y-R cDNA, RIKEN full-length enriched library, clone:I730084E05 product:trafficking protein particle complex 6B, full insert sequence
gi|74212152|dbj|AK168294.1|

Nucleotide
Chain 1, GLUTAMINE PHOSPHORIBOSYL-PYROPHOSPHATE AMIDOTRANSFERASE
Chain 1, GLUTAMINE PHOSPHORIBOSYL-PYROPHOSPHATE AMIDOTRANSFERASE
gi|576138|pdb|1GPH|1

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000546818	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 9, 2024)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 31871109, 28492532
SCV002079036	Natera, Inc.	no assertion criteria provided	Uncertain significance (Jan 23, 2020)	germline	clinical testing

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000546818

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 9, 2024)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

SCV002079036

Natera, Inc.

no assertion criteria provided

Uncertain significance
(Jan 23, 2020)

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

Prevalence of Inherited Mutations in Breast Cancer Predisposition Genes among Women in Uganda and Cameroon.

Adedokun B, Zheng Y, Ndom P, Gakwaya A, Makumbi T, Zhou AY, Yoshimatsu TF, Rodriguez A, Madduri RK, Foster IT, Sallam A, Olopade OI, Huo D.

Cancer Epidemiol Biomarkers Prev. 2020 Feb;29(2):359-367. doi: 10.1158/1055-9965.EPI-19-0506. Epub 2019 Dec 23.

PubMed [citation]

PMID:: 31871109
PMCID:: PMC7007381

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

Details of each submission

From Invitae, SCV000546818.9

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 1248 of the ATM protein (p.Tyr1248Cys). This variant is present in population databases (rs766226370, gnomAD 0.003%). This missense change has been observed in individual(s) with breast cancer (PMID: 31871109). ClinVar contains an entry for this variant (Variation ID: 407541). 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., SCV002079036.1

#	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: Aug 11, 2024

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