NM_000051.4(ATM):c.7897T>G (p.Leu2633Val) AND not provided

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Aug 10, 2021
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000115257.12

Allele description [Variation Report for NM_000051.4(ATM):c.7897T>G (p.Leu2633Val)]

NM_000051.4(ATM):c.7897T>G (p.Leu2633Val)

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.7897T>G (p.Leu2633Val)

Other names:

p.L2633V:TTA>GTA

HGVS:

NC_000011.10:g.108332870T>G
NG_009830.1:g.115039T>G
NG_054724.1:g.141963A>C
NM_000051.4:c.7897T>GMANE SELECT
NM_001330368.2:c.641-23799A>C
NM_001351110.2:c.*38+2350A>C
NM_001351834.2:c.7897T>G
NP_000042.3:p.Leu2633Val
NP_000042.3:p.Leu2633Val
NP_001338763.1:p.Leu2633Val
LRG_135t1:c.7897T>G
LRG_135:g.115039T>G
LRG_135p1:p.Leu2633Val
NC_000011.9:g.108203597T>G
NM_000051.3:c.7897T>G

Protein change:

L2633V

Links:

dbSNP: rs587779868

NCBI 1000 Genomes Browser:

rs587779868

Molecular consequence:

NM_001330368.2:c.641-23799A>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001351110.2:c.*38+2350A>C - intron variant - [Sequence Ontology: SO:0001627]
NM_000051.4:c.7897T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001351834.2:c.7897T>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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
SCV000149166	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Uncertain significance (Oct 9, 2013)	germline	clinical testing	Citation Link,
SCV002774795	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Uncertain significance (Aug 10, 2021)	unknown	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

SCV000149166

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Uncertain significance
(Oct 9, 2013)

germline

clinical testing

Citation Link,

SCV002774795

Quest Diagnostics Nichols Institute San Juan Capistrano

criteria provided, single submitter

(Quest Diagnostics criteria)

Uncertain significance
(Aug 10, 2021)

unknown

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
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

A Standardized DNA Variant Scoring System for Pathogenicity Assessments in Mendelian Disorders.

Karbassi I, Maston GA, Love A, DiVincenzo C, Braastad CD, Elzinga CD, Bright AR, Previte D, Zhang K, Rowland CM, McCarthy M, Lapierre JL, Dubois F, Medeiros KA, Batish SD, Jones J, Liaquat K, Hoffman CA, Jaremko M, Wang Z, Sun W, Buller-Burckle A, et al.

Hum Mutat. 2016 Jan;37(1):127-34. doi: 10.1002/humu.22918. Epub 2015 Oct 29.

PubMed [citation]

PMID:: 26467025
PMCID:: PMC4737317

Details of each submission

From GeneDx, SCV000149166.11

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

Description

This variant is denoted c.7897T>G at the cDNA level or p.Leu2633Val (L2633V) at the protein level. This variant results in the replacement of a Leucine codon (TTA) with a Valine codon (GTA) at amino acid position 2633 of the ATM gene. The Leu2633Val missense substitution has not been published as a mutation, nor has it been reported as a polymorphism to our knowledge. The NHLBI Exome Sequencing Project reports Leu2633Val was not observed in approximately 6500 samples from individuals of European and African American backgrounds, indicating it is not a common benign variant in these populations. The Leu2633Val variant is a conservative substitution as a neutral Leucine residue is replaced by a neutral Valine residue at a position that is evolutionarily moderately conserved across species and is not located in a known functional domain. Additionally, in silico models are consistent in their prediction of a benign effect on protein structure and function. Based on the currently available information, we consider Leu2633Val to be a variant of 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

From Quest Diagnostics Nichols Institute San Juan Capistrano, SCV002774795.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	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