NM_000051.4(ATM):c.6095G>A (p.Arg2032Lys) AND not provided

Germline classification:: Pathogenic (4 submissions)
Last evaluated:: Dec 1, 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:: RCV000212037.28

Allele description [Variation Report for NM_000051.4(ATM):c.6095G>A (p.Arg2032Lys)]

NM_000051.4(ATM):c.6095G>A (p.Arg2032Lys)

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.6095G>A (p.Arg2032Lys)

Other names:

p.R2032K:AGA>AAA

HGVS:

NC_000011.10:g.108315911G>A
NG_009830.1:g.98080G>A
NG_054724.1:g.158922C>T
NM_000051.4:c.6095G>AMANE SELECT
NM_001330368.2:c.641-6840C>T
NM_001351110.2:c.*39-6840C>T
NM_001351834.2:c.6095G>A
NP_000042.3:p.Arg2032Lys
NP_000042.3:p.Arg2032Lys
NP_001338763.1:p.Arg2032Lys
LRG_135t1:c.6095G>A
LRG_135:g.98080G>A
LRG_135p1:p.Arg2032Lys
NC_000011.9:g.108186638G>A
NM_000051.3:c.6095G>A
p.R2032K

Protein change:

R2032K

Links:

dbSNP: rs139770721

NCBI 1000 Genomes Browser:

rs139770721

Molecular consequence:

NM_001330368.2:c.641-6840C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001351110.2:c.*39-6840C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_000051.4:c.6095G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001351834.2:c.6095G>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

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
SCV000209757	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Apr 27, 2023)	germline	clinical testing	Citation Link,
SCV000928203	Blueprint Genetics	criteria provided, single submitter (Blueprint Genetics Variant Classification Scheme)	Pathogenic (Feb 5, 2019)	germline	clinical testing	Citation Link,
SCV003916783	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Pathogenic (Dec 1, 2023)	germline	clinical testing	Citation Link,
SCV005199615	Clinical Genetics Laboratory, Skane University Hospital Lund	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (May 27, 2022)	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	5	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 GeneDx, SCV000209757.17

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

Description

Alters the last nucleotide of the exon in a gene for which loss-of-function is a known mechanism of disease, and published functional studies and splice predictors support a deleterious effect (Telatar et al., 1998); Observed in the heterozygous state in individuals with ATM-related and other cancers (Thorstenson et al., 2003; Roberts et al., 2012; Huang et al., 2015; Yurgelun et al., 2015; Podralska et al., 2018; Waszak et al., 2018; Schubert et al., 2019); Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 15390180, 32875559, 28888541, 31921190, 20153123, 22585167, 12810666, 10817650, 10980530, 25980754, 26506520, 27878467, 29678143, 9443866, 10330348, 16266405, 27159176, 25614872, 9887333, 29753700, 30426508, 30772474, 23532176, 29625052, 31447099, 33077847, 34522244, 29922827, 34308104)

#	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 Blueprint Genetics, SCV000928203.1

#	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	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From CeGaT Center for Human Genetics Tuebingen, SCV003916783.13

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	5	not provided	not provided	clinical testing	not provided

Description

ATM: PM3:Strong, PS3, PM2, PP3

#	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		5	not provided	not provided	not provided

From Clinical Genetics Laboratory, Skane University Hospital Lund, SCV005199615.1

#	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	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Nov 3, 2024

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