NM_000051.4(ATM):c.7867C>A (p.Leu2623Ile) AND Ataxia-telangiectasia syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 17, 2021
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:: RCV001875983.12

Allele description [Variation Report for NM_000051.4(ATM):c.7867C>A (p.Leu2623Ile)]

NM_000051.4(ATM):c.7867C>A (p.Leu2623Ile)

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.7867C>A (p.Leu2623Ile)

HGVS:

NC_000011.10:g.108332840C>A
NG_009830.1:g.115009C>A
NG_054724.1:g.141993G>T
NM_000051.4:c.7867C>AMANE SELECT
NM_001330368.2:c.641-23769G>T
NM_001351110.2:c.*38+2380G>T
NM_001351834.2:c.7867C>A
NP_000042.3:p.Leu2623Ile
NP_000042.3:p.Leu2623Ile
NP_001338763.1:p.Leu2623Ile
LRG_135t1:c.7867C>A
LRG_135:g.115009C>A
LRG_135p1:p.Leu2623Ile
NC_000011.9:g.108203567C>A
NC_000011.9:g.108203567C>A
NM_000051.3:c.7867C>A

Protein change:

L2623I

Links:

dbSNP: rs774118570

NCBI 1000 Genomes Browser:

rs774118570

Molecular consequence:

NM_001330368.2:c.641-23769G>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001351110.2:c.*38+2380G>T - intron variant - [Sequence Ontology: SO:0001627]
NM_000051.4:c.7867C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001351834.2:c.7867C>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

Recent activity

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RecName: Full=3-hydroxy-3-methylglutaryl-CoA lyase, cytoplasmic; AltName: Full=3...
RecName: Full=3-hydroxy-3-methylglutaryl-CoA lyase, cytoplasmic; AltName: Full=3-hydroxy-3-methylglutaryl-CoA lyase-like protein 1; Short=HMGCL-like 1; AltName: Full=Endoplasmic reticulum 3-hydroxy-3-methylglutaryl-CoA lyase; Short=er-cHL
gi|189028466|sp|Q8TB92.3|HMGC2_HUMA

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002256190	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 17, 2021)	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

SCV002256190

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 17, 2021)

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, SCV002256190.3

#	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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt ATM protein function. ClinVar contains an entry for this variant (Variation ID: 921131). This variant has not been reported in the literature in individuals affected with ATM-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.01%). This sequence change replaces leucine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 2623 of the ATM protein (p.Leu2623Ile).

#	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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