NM_000051.4(ATM):c.610G>A (p.Gly204Arg) AND not provided

Germline classification:: Uncertain significance (8 submissions)
Last evaluated:: Mar 13, 2024
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:: RCV000235097.47

Allele description [Variation Report for NM_000051.4(ATM):c.610G>A (p.Gly204Arg)]

NM_000051.4(ATM):c.610G>A (p.Gly204Arg)

Gene:

ATM:ATM serine/threonine kinase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

11q22.3

Genomic location:

Preferred name:

NM_000051.4(ATM):c.610G>A (p.Gly204Arg)

Other names:

p.G204R:GGA>AGA

HGVS:

NC_000011.10:g.108244066G>A
NG_009830.1:g.26235G>A
NM_000051.4:c.610G>AMANE SELECT
NM_001351834.2:c.610G>A
NP_000042.3:p.Gly204Arg
NP_000042.3:p.Gly204Arg
NP_001338763.1:p.Gly204Arg
LRG_135t1:c.610G>A
LRG_135:g.26235G>A
LRG_135p1:p.Gly204Arg
NC_000011.9:g.108114793G>A
NM_000051.3:c.610G>A
p.G204R

Protein change:

G204R

Links:

dbSNP: rs147915571

NCBI 1000 Genomes Browser:

rs147915571

Molecular consequence:

NM_000051.4:c.610G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001351834.2:c.610G>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
SCV000149133	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (Mar 13, 2024)	germline	clinical testing	Citation Link,
SCV000780399	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Uncertain significance (Dec 1, 2017)	germline	clinical testing	Citation Link,
SCV000861881	Eurofins Ntd Llc (ga)	criteria provided, single submitter (EGL ClinVar v180209 classification definitions)	Uncertain significance (Jun 11, 2018)	germline	clinical testing	Citation Link,
SCV002036912	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) - VKGL Data-share Consensus See additional submitters Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	no assertion criteria provided	Uncertain significance	germline	clinical testing
SCV002037469	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ - VKGL Data-share Consensus See additional submitters Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	no assertion criteria provided	Uncertain significance	germline	clinical testing
SCV004221216	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Uncertain significance (Apr 18, 2023)	unknown	clinical testing	PubMed (16) [See all records that cite these PMIDs] 30306255, 29522266, 29470806, 28779002, 28652578, 27720647, 26837699, 26580448, 25186627, 20305132, 34204722, 33471991, 33436325, 30303537, 31206626, 26467025
SCV004229281	Athena Diagnostics	criteria provided, single submitter (Athena Diagnostics Criteria)	Uncertain significance (Apr 18, 2023)	unknown	clinical testing	PubMed (16) [See all records that cite these PMIDs] 30306255, 29522266, 29470806, 28779002, 28652578, 27720647, 26837699, 26580448, 25186627, 20305132, 34204722, 33471991, 33436325, 30303537, 31206626, 26467025
SCV005412449	Mayo Clinic Laboratories, Mayo Clinic	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Aug 18, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 34326862, 35451682, 25741868

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	5	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

Multigene panel testing beyond BRCA1/2 in breast/ovarian cancer Spanish families and clinical actionability of findings.

Bonache S, Esteban I, Moles-Fernández A, Tenés A, Duran-Lozano L, Montalban G, Bach V, Carrasco E, Gadea N, López-Fernández A, Torres-Esquius S, Mancuso F, Caratú G, Vivancos A, Tuset N, Balmaña J, Gutiérrez-Enríquez S, Diez O.

J Cancer Res Clin Oncol. 2018 Dec;144(12):2495-2513. doi: 10.1007/s00432-018-2763-9. Epub 2018 Oct 10.

PubMed [citation]

PMID:: 30306255

Gene panel testing of 5589 BRCA1/2-negative index patients with breast cancer in a routine diagnostic setting: results of the German Consortium for Hereditary Breast and Ovarian Cancer.

Hauke J, Horvath J, Groß E, Gehrig A, Honisch E, Hackmann K, Schmidt G, Arnold N, Faust U, Sutter C, Hentschel J, Wang-Gohrke S, Smogavec M, Weber BHF, Weber-Lassalle N, Weber-Lassalle K, Borde J, Ernst C, Altmüller J, Volk AE, Thiele H, Hübbel V, et al.

Cancer Med. 2018 Apr;7(4):1349-1358. doi: 10.1002/cam4.1376. Epub 2018 Mar 9.

PubMed [citation]

PMID:: 29522266
PMCID:: PMC5911592

See all PubMed Citations (19)

Details of each submission

From GeneDx, SCV000149133.18

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

Description

In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 28779002, 24356096, 27720647, 26580448, 26837699, 28873162, 29470806, 29522266, 25186627, 20305132, 33436325, 34204722, 30303537, 30306255, 28652578, 33471991, 31206626, 34250389, 36685941, 35451682, 34326862)

#	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, SCV000780399.29

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

From Eurofins Ntd Llc (ga), SCV000861881.1

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

From Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) - VKGL Data-share Consensus, SCV002036912.1

#	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 Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ - VKGL Data-share Consensus, SCV002037469.1

#	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 Quest Diagnostics Nichols Institute San Juan Capistrano, SCV004221216.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (16)

Description

The frequency of this variant in the general population, 0.00023 (8/35374 chromosomes, http://gnomad.broadinstitute.org), is uninformative in assessment of its pathogenicity. In the published literature, the variant has been reported in individuals/families with breast and/or ovarian cancer (PMIDs: 34204722 (2021), 31206626 (2019), 29470806 (2018), 29522266 (2018), 30306255 (2018), 28779002 (2017), 25186627 (2015), 20305132 (2010)), lymphocytic leukemia (PMIDs: 28652578 (2017), 26837699 (2016)), rhabdomyosarcoma (PMID: 26580448 (2015)), and prostate cancer (PMID: 33436325 (2021). The variant has also been observed in healthy controls (PMIDs: 33436325 (2021), 30303537 (2019), 31206626 (2019), 28652578 (2017), 28779002 (2017)). In an individual with breast cancer, this variant co-occurred with a pathogenic variant in the BRCA1 gene, suggesting it may not be the cause of disease (PMID: 25186627 (2015)). Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded conflicting predictions that this variant is benign or damaging. Based on the available information, we are unable to determine the clinical significance of this variant.

#	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 Athena Diagnostics, SCV004229281.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (16)

Description

Available data are insufficient to determine the clinical significance of the variant at this time. The frequency of this variant in the general population is uninformative in assessment of its pathogenicity (http://gnomad.broadinstitute.org). Computational tools disagree on the variant's effect on normal protein function.

#	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, SCV005412449.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	4	not provided	not provided	clinical testing	PubMed (3)

Description

BP4

#	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		4	not provided	not provided	not provided

Last Updated: Nov 24, 2024

Relating variation to medicine