NM_001282225.2(ADA2):c.973-2A>G AND not provided

Germline classification:: Pathogenic (6 submissions)
Last evaluated:: Jun 29, 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:: RCV001091903.39

Allele description [Variation Report for NM_001282225.2(ADA2):c.973-2A>G]

NM_001282225.2(ADA2):c.973-2A>G

Gene:

ADA2:adenosine deaminase 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

22q11.1

Genomic location:

Preferred name:

NM_001282225.2(ADA2):c.973-2A>G

HGVS:

NC_000022.11:g.17188449T>C
NG_033943.1:g.38406A>G
NG_144784.1:g.605T>C
NG_144785.1:g.103T>C
NM_001282225.2:c.973-2A>GMANE SELECT
NM_001282226.2:c.973-2A>G
NM_001282227.2:c.847-2A>G
NM_001282228.2:c.847-2A>G
NM_001282229.2:c.613-2A>G
NM_177405.3:c.250-2A>G
LRG_1217t1:c.973-2A>G
LRG_1217:g.38406A>G
NC_000022.10:g.17669339T>C
NM_001282225.1:c.973-2A>G

Links:

dbSNP: rs139750129

NCBI 1000 Genomes Browser:

rs139750129

Molecular consequence:

NM_001282225.2:c.973-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001282226.2:c.973-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001282227.2:c.847-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001282228.2:c.847-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001282229.2:c.613-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_177405.3:c.250-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]

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
SCV001248182	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Pathogenic (Jan 1, 2023)	germline	clinical testing	Citation Link,
SCV001713078	Mayo Clinic Laboratories, Mayo Clinic	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Mar 17, 2020)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 28493328, 29963054, 29391253, 25741868
SCV001790149	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Jun 29, 2024)	germline	clinical testing	Citation Link,
SCV001807159	Genome Diagnostics Laboratory, Amsterdam University Medical Center - VKGL Data-share Consensus	no assertion criteria provided	Likely pathogenic	germline	clinical testing
SCV001930101	Genome Diagnostics Laboratory, University Medical Center Utrecht - VKGL Data-share Consensus See additional submitters Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	no assertion criteria provided	Pathogenic	germline	clinical testing
SCV001952218	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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	6	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Screening of 181 Patients With Antibody Deficiency for Deficiency of Adenosine Deaminase 2 Sheds New Light on the Disease in Adulthood.

Schepp J, Proietti M, Frede N, Buchta M, Hübscher K, Rojas Restrepo J, Goldacker S, Warnatz K, Pachlopnik Schmid J, Duppenthaler A, Lougaris V, Uriarte I, Kelly S, Hershfield M, Grimbacher B.

Arthritis Rheumatol. 2017 Aug;69(8):1689-1700. doi: 10.1002/art.40147. Epub 2017 Jul 5.

PubMed [citation]

PMID:: 28493328

Deficiency of Adenosine Deaminase 2 in Adult Siblings: Many Years of a Misdiagnosed Disease With Severe Consequences.

Springer JM, Gierer SA, Jiang H, Kleiner D, Deuitch N, Ombrello AK, Grayson PC, Aksentijevich I.

Front Immunol. 2018;9:1361. doi: 10.3389/fimmu.2018.01361.

PubMed [citation]

PMID:: 29963054
PMCID:: PMC6010516

See all PubMed Citations (4)

Details of each submission

From CeGaT Center for Human Genetics Tuebingen, SCV001248182.26

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	6	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		6	not provided	not provided	not provided

From Mayo Clinic Laboratories, Mayo Clinic, SCV001713078.1

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

Description

PVS1, PP1_strong, PS4_moderate, PP4

#	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 GeneDx, SCV001790149.2

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

Description

Published functional studies demonstrate a damaging effect. This splice site variant destroys the canonical splice acceptor site in intron 6. It is predicted to cause abnormal gene splicing, either leading to an abnormal message that is subject to nonsense-mediated mRNA decay, or to an abnormal protein product if the message is used for protein translation (PMID: 29963054); Canonical splice site variant predicted to result in a null allele in a gene for which loss of function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 31393689, 31856934, 29391253, 28983775, 30386947, 29681619, 28493328, 31617030, 32535845, 34039731, 29963054)

#	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 Genome Diagnostics Laboratory, Amsterdam University Medical Center - VKGL Data-share Consensus, SCV001807159.1

#	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 Genome Diagnostics Laboratory, University Medical Center Utrecht - VKGL Data-share Consensus, SCV001930101.1

#	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, SCV001952218.1

#	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

Last Updated: Nov 24, 2024

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