NM_000051.4(ATM):c.6411C>G (p.Asp2137Glu) AND not provided

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Aug 9, 2023
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:: RCV000590406.12

Allele description [Variation Report for NM_000051.4(ATM):c.6411C>G (p.Asp2137Glu)]

NM_000051.4(ATM):c.6411C>G (p.Asp2137Glu)

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.6411C>G (p.Asp2137Glu)

HGVS:

NC_000011.10:g.108320017C>G
NG_009830.1:g.102186C>G
NG_054724.1:g.154816G>C
NM_000051.4:c.6411C>GMANE SELECT
NM_001330368.2:c.641-10946G>C
NM_001351110.2:c.*39-10946G>C
NM_001351834.2:c.6411C>G
NP_000042.3:p.Asp2137Glu
NP_000042.3:p.Asp2137Glu
NP_001338763.1:p.Asp2137Glu
LRG_135t1:c.6411C>G
LRG_135:g.102186C>G
LRG_135p1:p.Asp2137Glu
NC_000011.9:g.108190744C>G
NM_000051.3:c.6411C>G

Protein change:

D2137E

Links:

dbSNP: rs780299607

NCBI 1000 Genomes Browser:

rs780299607

Molecular consequence:

NM_001330368.2:c.641-10946G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001351110.2:c.*39-10946G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_000051.4:c.6411C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001351834.2:c.6411C>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000564651	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (Aug 9, 2023)	germline	clinical testing	Citation Link,
SCV000694323	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Uncertain significance (Mar 16, 2017)	germline	clinical testing	LabCorp Variant Classification Summary - May 2015.docx Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000564651

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Uncertain significance
(Aug 9, 2023)

germline

clinical testing

Citation Link,

SCV000694323

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Uncertain significance
(Mar 16, 2017)

germline

clinical testing

LabCorp Variant Classification Summary - May 2015.docx

Citation Link

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

Details of each submission

From GeneDx, SCV000564651.3

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

Description

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 23532176)

#	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 Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000694323.1

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

Description

Variant summary: The ATM c.6411C>G (p.Asp2137Glu) variant involves the alteration of a non-conserved nucleotide. 2/4 in silico tools predict a damaging outcome for this variant (SNPs&GO and MutationTaster not captured due to low reliability index). This variant was found in 1/121172 control chromosomes at a frequency of 0.0000083, which does not exceed the estimated maximal expected allele frequency of a pathogenic ATM variant (0.0010005). One clinical diagnostic laboratory has classified this variant as uncertain significance. The variant of interest has not, to our knowledge, been reported in affected individuals via publications nor evaluated for functional impact by in vivo/vitro studies. Because of the absence of clinical information and the lack of functional studies, the variant is classified as a variant of uncertain significance (VUS) until additional information becomes available.

#	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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