NM_000051.4(ATM):c.6391G>C (p.Ala2131Pro) AND Ataxia-telangiectasia syndrome

Germline classification:: Uncertain significance (1 submission)
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:: RCV003340947.2

Allele description [Variation Report for NM_000051.4(ATM):c.6391G>C (p.Ala2131Pro)]

NM_000051.4(ATM):c.6391G>C (p.Ala2131Pro)

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.6391G>C (p.Ala2131Pro)

HGVS:

NC_000011.10:g.108319997G>C
NG_009830.1:g.102166G>C
NG_054724.1:g.154836C>G
NM_000051.4:c.6391G>CMANE SELECT
NM_001330368.2:c.641-10926C>G
NM_001351110.2:c.*39-10926C>G
NM_001351834.2:c.6391G>C
NP_000042.3:p.Ala2131Pro
NP_000042.3:p.Ala2131Pro
NP_001338763.1:p.Ala2131Pro
LRG_135t1:c.6391G>C
LRG_135:g.102166G>C
LRG_135p1:p.Ala2131Pro
NC_000011.9:g.108190724G>C
NM_000051.3:c.6391G>C

Protein change:

A2131P

Molecular consequence:

NM_001330368.2:c.641-10926C>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001351110.2:c.*39-10926C>G - intron variant - [Sequence Ontology: SO:0001627]
NM_000051.4:c.6391G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001351834.2:c.6391G>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
SCV004047831	Neuberg Centre For Genomic Medicine, NCGM	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance	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

SCV004047831

Neuberg Centre For Genomic Medicine, NCGM

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance

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	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Neuberg Centre For Genomic Medicine, NCGM, SCV004047831.1

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

Description

The missense variant c.6391G>C (p.Ala2131Pro) in ATM gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The p.Ala2131Pro variant is novel (not in any individuals) in gnomAD exomes and 1000 Genomes. This variant has not been reported to the ClinVar database. The amino acid Ala at position 2131 is changed to a Pro changing protein sequence and it might alter its composition and physico-chemical properties. The amino acid change p.Ala2131Pro in ATM is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Uncertain Significance.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Oct 26, 2024

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