NM_000051.4(ATM):c.7888T>G (p.Leu2630Val) AND Ataxia-telangiectasia syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 25, 2017
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:: RCV000548687.15

Allele description [Variation Report for NM_000051.4(ATM):c.7888T>G (p.Leu2630Val)]

NM_000051.4(ATM):c.7888T>G (p.Leu2630Val)

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.7888T>G (p.Leu2630Val)

HGVS:

NC_000011.10:g.108332861T>G
NG_009830.1:g.115030T>G
NG_054724.1:g.141972A>C
NM_000051.4:c.7888T>GMANE SELECT
NM_001330368.2:c.641-23790A>C
NM_001351110.2:c.*38+2359A>C
NM_001351834.2:c.7888T>G
NP_000042.3:p.Leu2630Val
NP_000042.3:p.Leu2630Val
NP_001338763.1:p.Leu2630Val
LRG_135t1:c.7888T>G
LRG_135:g.115030T>G
LRG_135p1:p.Leu2630Val
NC_000011.9:g.108203588T>G
NM_000051.3:c.7888T>G

Protein change:

L2630V

Links:

dbSNP: rs1555125427

NCBI 1000 Genomes Browser:

rs1555125427

Molecular consequence:

NM_001330368.2:c.641-23790A>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001351110.2:c.*38+2359A>C - intron variant - [Sequence Ontology: SO:0001627]
NM_000051.4:c.7888T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001351834.2:c.7888T>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
SCV000622783	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 25, 2017)	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

SCV000622783

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 25, 2017)

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, SCV000622783.4

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

Description

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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with ATM-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces leucine with valine at codon 2630 of the ATM protein (p.Leu2630Val). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and valine.

#	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: Nov 10, 2024

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