NM_000051.4(ATM):c.6420C>G (p.Phe2140Leu) AND Ataxia-telangiectasia syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 30, 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:: RCV001990620.12

Allele description [Variation Report for NM_000051.4(ATM):c.6420C>G (p.Phe2140Leu)]

NM_000051.4(ATM):c.6420C>G (p.Phe2140Leu)

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.6420C>G (p.Phe2140Leu)

HGVS:

NC_000011.10:g.108320026C>G
NG_009830.1:g.102195C>G
NG_054724.1:g.154807G>C
NM_000051.4:c.6420C>GMANE SELECT
NM_001330368.2:c.641-10955G>C
NM_001351110.2:c.*39-10955G>C
NM_001351834.2:c.6420C>G
NP_000042.3:p.Phe2140Leu
NP_000042.3:p.Phe2140Leu
NP_001338763.1:p.Phe2140Leu
LRG_135t1:c.6420C>G
LRG_135:g.102195C>G
LRG_135p1:p.Phe2140Leu
NC_000011.9:g.108190753C>G
NM_000051.3:c.6420C>G

Protein change:

F2140L

Links:

dbSNP: rs587780635

NCBI 1000 Genomes Browser:

rs587780635

Molecular consequence:

NM_001330368.2:c.641-10955G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001351110.2:c.*39-10955G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_000051.4:c.6420C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001351834.2:c.6420C>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

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
SCV002253073	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 30, 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

SCV002253073

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 30, 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, SCV002253073.3

#	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 not expected to disrupt ATM protein function. This variant has not been reported in the literature in individuals affected with ATM-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces phenylalanine with leucine at codon 2140 of the ATM protein (p.Phe2140Leu). The phenylalanine residue is moderately conserved and there is a small physicochemical difference between phenylalanine and leucine.

#	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 3, 2024

ClinVar

Relating variation to medicine