NM_000051.4(ATM):c.6418T>C (p.Phe2140Leu) AND Ataxia-telangiectasia syndrome

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Dec 9, 2023
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:: RCV000806982.18

Allele description [Variation Report for NM_000051.4(ATM):c.6418T>C (p.Phe2140Leu)]

NM_000051.4(ATM):c.6418T>C (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.6418T>C (p.Phe2140Leu)

HGVS:

NC_000011.10:g.108320024T>C
NG_009830.1:g.102193T>C
NG_054724.1:g.154809A>G
NM_000051.4:c.6418T>CMANE SELECT
NM_001330368.2:c.641-10953A>G
NM_001351110.2:c.*39-10953A>G
NM_001351834.2:c.6418T>C
NP_000042.3:p.Phe2140Leu
NP_000042.3:p.Phe2140Leu
NP_001338763.1:p.Phe2140Leu
LRG_135t1:c.6418T>C
LRG_135:g.102193T>C
LRG_135p1:p.Phe2140Leu
NC_000011.9:g.108190751T>C
NM_000051.3:c.6418T>C

Protein change:

F2140L

Links:

dbSNP: rs1397647612

NCBI 1000 Genomes Browser:

rs1397647612

Molecular consequence:

NM_001330368.2:c.641-10953A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001351110.2:c.*39-10953A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_000051.4:c.6418T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001351834.2:c.6418T>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
SCV000947006	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 9, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 33646313, 35171259, 28492532
SCV002084308	Natera, Inc.	no assertion criteria provided	Uncertain significance (Dec 14, 2020)	germline	clinical testing

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000947006

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 9, 2023)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

SCV002084308

Natera, Inc.

no assertion criteria provided

Uncertain significance
(Dec 14, 2020)

germline

clinical testing

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

Gene Sequencing for Pathogenic Variants Among Adults With Breast and Ovarian Cancer in the Caribbean.

George SHL, Donenberg T, Alexis C, DeGennaro V Jr, Dyer H, Yin S, Ali J, Butler R, Chin SN, Curling D, Lowe D, Lunn J, Turnquest T, Wharfe G, Cerbon D, Barreto-Coelho P, Schlumbrecht MP, Akbari MR, Narod SA, Hurley JE.

JAMA Netw Open. 2021 Mar 1;4(3):e210307. doi: 10.1001/jamanetworkopen.2021.0307.

PubMed [citation]

PMID:: 33646313
PMCID:: PMC7921902

Prevalence of Germline Sequence Variations Among Patients With Pancreatic Cancer in China.

Yin L, Wei J, Lu Z, Huang S, Gao H, Chen J, Guo F, Tu M, Xiao B, Xi C, Zhang K, Li Q, Wu J, Gao W, Jiang K, Yu J, Miao Y.

JAMA Netw Open. 2022 Feb 1;5(2):e2148721. doi: 10.1001/jamanetworkopen.2021.48721.

PubMed [citation]

PMID:: 35171259
PMCID:: PMC8851306

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000947006.5

#	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 phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 2140 of the ATM protein (p.Phe2140Leu). This variant is present in population databases (no rsID available, gnomAD 0.003%). This missense change has been observed in individual(s) with pancreatic ductal adenocarcinoma, breast and/or ovarian cancer (PMID: 33646313, 35171259). ClinVar contains an entry for this variant (Variation ID: 489571). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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

From Natera, Inc., SCV002084308.1

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

#	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

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