NM_000051.4(ATM):c.331+5G>A AND not provided

Germline classification:: Pathogenic/Likely pathogenic (6 submissions)
Last evaluated:: Oct 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:: RCV000761802.31

Allele description [Variation Report for NM_000051.4(ATM):c.331+5G>A]

NM_000051.4(ATM):c.331+5G>A

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.331+5G>A

HGVS:

NC_000011.10:g.108229328G>A
NG_009830.1:g.11497G>A
NM_000051.4:c.331+5G>AMANE SELECT
NM_001351834.2:c.331+5G>A
NM_001351835.2:c.336G>A
NM_001351836.2:c.336G>A
NP_001338764.1:p.Lys112=
NP_001338765.1:p.Lys112=
LRG_135t1:c.331+5G>A
LRG_135:g.11497G>A
NC_000011.9:g.108100055G>A
NM_000051.3:c.331+5G>A

Links:

dbSNP: rs752135143

NCBI 1000 Genomes Browser:

rs752135143

Molecular consequence:

NM_000051.4:c.331+5G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001351834.2:c.331+5G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001351835.2:c.336G>A - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001351836.2:c.336G>A - synonymous variant - [Sequence Ontology: SO:0001819]

Observations:

Condition(s)

Synonyms:: none provided; RECLASSIFIED - ADRA2C POLYMORPHISM; RECLASSIFIED - ADRB1 POLYMORPHISM
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000891999	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Likely pathogenic (Jul 1, 2018)	germline	clinical testing	Citation Link,
SCV001741181	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen - VKGL Data-share Consensus	no assertion criteria provided	Pathogenic	germline	clinical testing
SCV001906252	Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute - VKGL Data-share Consensus See additional submitters Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	no assertion criteria provided	Likely pathogenic	germline	clinical testing
SCV001958220	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	Pathogenic	germline	clinical testing
SCV004169100	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Oct 9, 2023)	germline	clinical testing	Citation Link,
SCV005199598	Clinical Genetics Laboratory, Skane University Hospital Lund	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Nov 18, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

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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

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 CeGaT Center for Human Genetics Tuebingen, SCV000891999.29

#	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 Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen - VKGL Data-share Consensus, SCV001741181.3

#	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 Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute - VKGL Data-share Consensus, SCV001906252.1

#	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, SCV001958220.1

#	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 GeneDx, SCV004169100.1

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

Description

Intronic variant directly or indirectly altering the +5 splice site in a gene for which loss of function is a known mechanism of disease, and published functional studies demonstrate this variant causes skipping of exon 4, with reduced or absent ATM protein and kinase activity (Verhagen et al., 2009; Verhagen et al., 2012; Nakamura et al., 2012; van Os et al., 2017); Observed in the homozygous or compound heterozygous state in several individuals with ataxia-telangiectasia (Verhagen et al., 2009; Verhagen et al., 2012; Nakamura et al., 2012; Chen et al., 2013; van Os et al., 2017); Observed in the heterozygous state in individuals with prostate or ovarian cancer (Lilyquist et al., 2017; Darst et al., 2021); Not observed at significant frequency in large population cohorts (gnomAD); Also reported as IVS6+5G>A using alternate intron nomenclature; This variant is associated with the following publications: (PMID: 23726790, 22006793, 19535770, 23566627, 22213089, 28126470, 19705055, 30549301, 29288088, 32853339, 29922827, 30850667, 37649078, 28888541)

#	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 Clinical Genetics Laboratory, Skane University Hospital Lund, SCV005199598.1

#	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: Dec 22, 2024

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