NM_000051.4(ATM):c.2818A>G (p.Lys940Glu) AND Ataxia-telangiectasia syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 31, 2023
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:: RCV000549701.8

Allele description [Variation Report for NM_000051.4(ATM):c.2818A>G (p.Lys940Glu)]

NM_000051.4(ATM):c.2818A>G (p.Lys940Glu)

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.2818A>G (p.Lys940Glu)

HGVS:

NC_000011.10:g.108268589A>G
NG_009830.1:g.50758A>G
NM_000051.4:c.2818A>GMANE SELECT
NM_001351834.2:c.2818A>G
NP_000042.3:p.Lys940Glu
NP_000042.3:p.Lys940Glu
NP_001338763.1:p.Lys940Glu
LRG_135t1:c.2818A>G
LRG_135:g.50758A>G
LRG_135p1:p.Lys940Glu
NC_000011.9:g.108139316A>G
NM_000051.3:c.2818A>G

Protein change:

K940E

Links:

dbSNP: rs1064795896

NCBI 1000 Genomes Browser:

rs1064795896

Molecular consequence:

NM_000051.4:c.2818A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001351834.2:c.2818A>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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Drosophila melanogaster uncharacterized protein (CG15042), mRNA
Drosophila melanogaster uncharacterized protein (CG15042), mRNA
gi|320542305|ref|NM_133080.2|

Nucleotide
Mus musculus SMAD specific E3 ubiquitin protein ligase 2 (Smurf2), transcript va...
Mus musculus SMAD specific E3 ubiquitin protein ligase 2 (Smurf2), transcript variant 1, mRNA
gi|1386635289|ref|NM_025481.3|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000622364	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 31, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 30426508, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000622364

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 31, 2023)

germline

clinical testing

PubMed (2)
[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	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

The identification of pathogenic variants in BRCA1/2 negative, high risk, hereditary breast and/or ovarian cancer patients: High frequency of FANCM pathogenic variants.

Schubert S, van Luttikhuizen JL, Auber B, Schmidt G, Hofmann W, Penkert J, Davenport CF, Hille-Betz U, Wendeburg L, Bublitz J, Tauscher M, Hackmann K, Schröck E, Scholz C, Wallaschek H, Schlegelberger B, Illig T, Steinemann D.

Int J Cancer. 2019 Jun 1;144(11):2683-2694. doi: 10.1002/ijc.31992. Epub 2019 Jan 11.

PubMed [citation]

PMID:: 30426508

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV000622364.6

#	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 lysine, which is basic and polar, with glutamic acid, which is acidic and polar, at codon 940 of the ATM protein (p.Lys940Glu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with breast cancer (PMID: 30426508). ClinVar contains an entry for this variant (Variation ID: 422618). 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

Last Updated: Sep 29, 2024

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