NM_000051.4(ATM):c.7880A>C (p.Tyr2627Ser) AND Ataxia-telangiectasia syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 13, 2022
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:: RCV003091199.9

Allele description [Variation Report for NM_000051.4(ATM):c.7880A>C (p.Tyr2627Ser)]

NM_000051.4(ATM):c.7880A>C (p.Tyr2627Ser)

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.7880A>C (p.Tyr2627Ser)

HGVS:

NC_000011.10:g.108332853A>C
NG_009830.1:g.115022A>C
NG_054724.1:g.141980T>G
NM_000051.4:c.7880A>CMANE SELECT
NM_001330368.2:c.641-23782T>G
NM_001351110.2:c.*38+2367T>G
NM_001351834.2:c.7880A>C
NP_000042.3:p.Tyr2627Ser
NP_000042.3:p.Tyr2627Ser
NP_001338763.1:p.Tyr2627Ser
LRG_135t1:c.7880A>C
LRG_135:g.115022A>C
LRG_135p1:p.Tyr2627Ser
NC_000011.9:g.108203580A>C
NM_000051.3:c.7880A>C

Protein change:

Y2627S

Molecular consequence:

NM_001330368.2:c.641-23782T>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001351110.2:c.*38+2367T>G - intron variant - [Sequence Ontology: SO:0001627]
NM_000051.4:c.7880A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001351834.2:c.7880A>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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003474875	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 13, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 22071889, 27664052, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003474875

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 13, 2022)

germline

clinical testing

PubMed (3)
[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

Underexpression and abnormal localization of ATM products in ataxia telangiectasia patients bearing ATM missense mutations.

Jacquemin V, Rieunier G, Jacob S, Bellanger D, d'Enghien CD, Laugé A, Stoppa-Lyonnet D, Stern MH.

Eur J Hum Genet. 2012 Mar;20(3):305-12. doi: 10.1038/ejhg.2011.196. Epub 2011 Nov 9.

PubMed [citation]

PMID:: 22071889
PMCID:: PMC3283185

Molecular and Functional Characterization of a Cohort of Spanish Patients with Ataxia-Telangiectasia.

Carranza D, Vega AK, Torres-Rusillo S, Montero E, Martinez LJ, Santamaría M, Santos JL, Molina IJ.

Neuromolecular Med. 2017 Mar;19(1):161-174. doi: 10.1007/s12017-016-8440-8. Epub 2016 Sep 23.

PubMed [citation]

PMID:: 27664052

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003474875.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change replaces tyrosine, which is neutral and polar, with serine, which is neutral and polar, at codon 2627 of the ATM protein (p.Tyr2627Ser). This variant is present in population databases (no rsID available, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with ATM-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. This variant disrupts the p.Tyr2627 amino acid residue in ATM. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 22071889, 27664052). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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: Nov 10, 2024

ClinVar

Relating variation to medicine