NM_000051.4(ATM):c.6383T>C (p.Leu2128Ser) AND Ataxia-telangiectasia syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 19, 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:: RCV003607356.2

Allele description [Variation Report for NM_000051.4(ATM):c.6383T>C (p.Leu2128Ser)]

NM_000051.4(ATM):c.6383T>C (p.Leu2128Ser)

Genes:

ATM:ATM serine/threonine kinase [Gene - OMIM - HGNC]
C11orf65:chromosome 11 open reading frame 65 [Gene - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

11q22.3

Genomic location:

Preferred name:

NM_000051.4(ATM):c.6383T>C (p.Leu2128Ser)

HGVS:

NC_000011.10:g.108319989T>C
NG_009830.1:g.102158T>C
NG_054724.1:g.154844A>G
NM_000051.4:c.6383T>CMANE SELECT
NM_001330368.2:c.641-10918A>G
NM_001351110.2:c.*39-10918A>G
NM_001351834.2:c.6383T>C
NP_000042.3:p.Leu2128Ser
NP_000042.3:p.Leu2128Ser
NP_001338763.1:p.Leu2128Ser
LRG_135t1:c.6383T>C
LRG_135:g.102158T>C
LRG_135p1:p.Leu2128Ser
NC_000011.9:g.108190716T>C
NM_000051.3:c.6383T>C

Protein change:

L2128S

Links:

dbSNP: rs1565508867

NCBI 1000 Genomes Browser:

rs1565508867

Molecular consequence:

NM_001330368.2:c.641-10918A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001351110.2:c.*39-10918A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_000051.4:c.6383T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001351834.2:c.6383T>C - 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
SCV004551676	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 19, 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

SCV004551676

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 19, 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	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

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004551676.1

#	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 leucine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 2128 of the ATM protein (p.Leu2128Ser). This variant is not present in population databases (gnomAD no frequency). 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: 631338). 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

Last Updated: Oct 26, 2024

ClinVar

Relating variation to medicine