NM_000051.4(ATM):c.6067G>A (p.Gly2023Arg) AND not provided

Germline classification:: Conflicting interpretations of pathogenicity (11 submissions)
Last evaluated:: Aug 1, 2024
Review status:: criteria provided, conflicting classifications

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:: RCV000513642.52

Allele description [Variation Report for NM_000051.4(ATM):c.6067G>A (p.Gly2023Arg)]

NM_000051.4(ATM):c.6067G>A (p.Gly2023Arg)

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.6067G>A (p.Gly2023Arg)

Other names:

p.G2023R:GGA>AGA; NP_000042.3:p.Gly2023Arg

HGVS:

NC_000011.10:g.108315883G>A
NG_009830.1:g.98052G>A
NG_054724.1:g.158950C>T
NM_000051.4:c.6067G>AMANE SELECT
NM_001330368.2:c.641-6812C>T
NM_001351110.2:c.*39-6812C>T
NM_001351834.2:c.6067G>A
NP_000042.3:p.Gly2023Arg
NP_000042.3:p.Gly2023Arg
NP_001338763.1:p.Gly2023Arg
LRG_135t1:c.6067G>A
LRG_135:g.98052G>A
LRG_135p1:p.Gly2023Arg
NC_000011.9:g.108186610G>A
NM_000051.2:c.6067G>A
NM_000051.3:c.6067G>A
Q13315:p.Gly2023Arg
p.G2023R

Protein change:

G2023R

Links:

UniProtKB: Q13315#VAR_077238; dbSNP: rs11212587

NCBI 1000 Genomes Browser:

rs11212587

Molecular consequence:

NM_001330368.2:c.641-6812C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001351110.2:c.*39-6812C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_000051.4:c.6067G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001351834.2:c.6067G>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

157

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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N-acetylmuramoyl-L-alanine amidase, family 4 [Staphylococcus epidermidis NIHLM03...
N-acetylmuramoyl-L-alanine amidase, family 4 [Staphylococcus epidermidis NIHLM031]
gi|394273886|gb|EJE18313.1||gnl|WGS |HMPREF9980_00370

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000149130	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Likely benign (Jun 17, 2021)	germline	clinical testing	Citation Link,
SCV000608617	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Likely benign (Aug 1, 2024)	germline	clinical testing	Citation Link,
SCV000694314	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Benign (Aug 21, 2017)	germline	clinical testing	PubMed (17) [See all records that cite these PMIDs] 12149228, 26787654, 12810666, 26822949, 25625042, 11505391, 23091097, 21933854, 23555315, 26976419, 25980754, 26053404, 16461462, 17393301, 17968022, 19404735, 27621404 LabCorp Variant Classification Summary - May 2015.docx, Citation Link,
SCV000840948	Athena Diagnostics	criteria provided, single submitter (Athena Diagnostics Criteria)	Likely benign (Dec 19, 2019)	unknown	clinical testing	PubMed (21) [See all records that cite these PMIDs] 27621404, 19404735, 26094658, 24728327, 25625042, 11505391, 12810666, 17968022, 23091097, 17393301, 12149228, 16461462, 25980754, 27153395, 28608266, 26898890, 22529920, 19781682, 26976419, 27664052, 26467025
SCV001469357	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Likely benign (Apr 18, 2023)	unknown	clinical testing	PubMed (30) [See all records that cite these PMIDs] 27621404, 19404735, 26094658, 24728327, 25625042, 11505391, 12810666, 17968022, 23091097, 17393301, 12149228, 16461462, 25980754, 33280026, 26822949, 26787654, 23555315, 21933854, 27153395, 28608266, 26898890, 29678143, 22529920, 35264596, 35245693, 32854451, 19781682, 26976419, 27664052, 26467025
SCV001713581	Mayo Clinic Laboratories, Mayo Clinic	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Feb 17, 2023)	germline	clinical testing	PubMed (13) [See all records that cite these PMIDs] 11505391, 19404735, 22529920, 24728327, 25625042, 26094658, 29445900, 30613976, 31159747, 32854451, 35245693, 35264596, 25741868
SCV001971707	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center - VKGL Data-share Consensus See additional submitters Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	no assertion criteria provided	Likely benign	germline	clinical testing
SCV002010799	Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely benign (Nov 3, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV003800554	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process 2021)	Likely benign (Oct 20, 2022)	germline	clinical testing	Citation Link,
SCV004228873	GenomeConnect - Invitae Patient Insights Network	no classification provided	not provided	unknown	phenotyping only
SCV005199614	Clinical Genetics Laboratory, Skane University Hospital Lund	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely benign (Jun 10, 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	34	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	1	not provided	not provided	1	not provided	clinical testing, phenotyping only
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	122	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Comprehensive Analysis of Disease-Related Genes in Chronic Lymphocytic Leukemia by Multiplex PCR-Based Next Generation Sequencing.

Vollbrecht C, Mairinger FD, Koitzsch U, Peifer M, Koenig K, Heukamp LC, Crispatzu G, Wilden L, Kreuzer KA, Hallek M, Odenthal M, Herling CD, Buettner R.

PLoS One. 2015;10(6):e0129544. doi: 10.1371/journal.pone.0129544.

PubMed [citation]

PMID:: 26053404
PMCID:: PMC4459702

Conflicting Interpretation of Genetic Variants and Cancer Risk by Commercial Laboratories as Assessed by the Prospective Registry of Multiplex Testing.

Balmaña J, Digiovanni L, Gaddam P, Walsh MF, Joseph V, Stadler ZK, Nathanson KL, Garber JE, Couch FJ, Offit K, Robson ME, Domchek SM.

J Clin Oncol. 2016 Dec;34(34):4071-4078. Epub 2016 Sep 30.

PubMed [citation]

PMID:: 27621404
PMCID:: PMC5562435

See all PubMed Citations (35)

Details of each submission

From GeneDx, SCV000149130.16

#	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 associated with the following publications: (PMID: 26976419, 26787654, 26094658, 27153395, 21933854, 29445900, 26053404, 19404735, 11505391, 17393301, 12810666, 22529920, 23091097, 17968022, 12149228, 16461462, 21787400, 19781682, 24728327, 25624042, 26898890, 27664052, 25980754, 24584352, 27150160, 26483394, 26822149, 27882345, 25625042, 27498913, 28608266, 29678143, 23555315, 26822949, 27621404, 28779002, 30197789, 31108397, 30309722, 31159747, 30303537, 32854451)

#	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, SCV000608617.31

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	34	not provided	not provided	clinical testing	not provided

Description

ATM: BS1:Supporting

#	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		34	not provided	not provided	not provided

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000694314.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (17)

Description

Variant summary: The ATM c.6067G>A (p.Gly2023Arg) variant involves the alteration of a conserved nucleotide and 4/4 in silico tools predict a damaging outcome for this variant (SNPsandGO not captured due to low reliability index). This variant was found in 397/277154 (1 homozygote) control chromosomes (gnomAD), predominantly observed in the European (Non-Finnish) subpopulation at a frequency of 0.002368 (300/126680). This frequency is about 2 times the estimated maximal expected allele frequency of a pathogenic ATM variant (0.0010005), suggesting this is likely a benign polymorphism found primarily in the populations of European (Non-Finnish) origin. Multiple publications have cited the variant in affected BrC pts, along with multiple somatic occurrences in MCL and CLL pts. Skowronska_2012 suggestions, biallelic ATM inactivation in CLL patients was associated with disease progression and reduced survival. However, the variant has been reported to co-occur with a BRCA1 variant, although the exact variant was not indicated (Thorstenson_2003). In addition, two internal LCA samples report the variant to co-occur with a pathogenic ATM variant, c.6095G>A (p.Arg20232Lys) and BRCA1 variant, c.1326T>A (p.Cys442X). In addition, multiple clinical diagnostic laboratories cite the variant as "likely benign/benign." Taken together, this variant is classified as benign.

#	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 Athena Diagnostics, SCV000840948.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (21)

#	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

From Quest Diagnostics Nichols Institute San Juan Capistrano, SCV001469357.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (30)

#	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

From Mayo Clinic Laboratories, Mayo Clinic, SCV001713581.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	122	not provided	not provided	clinical testing	PubMed (13)

Description

BS1

#	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		122	not provided	not provided	not provided

From Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center - VKGL Data-share Consensus, SCV001971707.1

#	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 Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden, SCV002010799.3

#	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	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories, SCV003800554.2

#	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

From GenomeConnect - Invitae Patient Insights Network, SCV004228873.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	phenotyping only	not provided

Description

Variant interpreted as Uncertain significance and reported on 02-18-2016 by Lab GenPath. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	1	not provided	not provided		1	not provided	not provided	not provided

From Clinical Genetics Laboratory, Skane University Hospital Lund, SCV005199614.1

#	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: Oct 26, 2024

Relating variation to medicine