NM_000022.4(ADA):c.646G>A (p.Gly216Arg) AND not provided

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Mar 1, 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:: RCV000256171.10

Allele description [Variation Report for NM_000022.4(ADA):c.646G>A (p.Gly216Arg)]

NM_000022.4(ADA):c.646G>A (p.Gly216Arg)

Gene:

ADA:adenosine deaminase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

20q13.12

Genomic location:

Preferred name:

NM_000022.4(ADA):c.646G>A (p.Gly216Arg)

Other names:

NM_000022.4(ADA):c.646G>A

HGVS:

NC_000020.11:g.44623039C>T
NG_007385.1:g.33697G>A
NM_000022.4:c.646G>AMANE SELECT
NM_001322050.2:c.241G>A
NM_001322051.2:c.607-109G>A
NP_000013.2:p.Gly216Arg
NP_001308979.1:p.Gly81Arg
LRG_16:g.33697G>A
NC_000020.10:g.43251680C>T
NM_000022.3:c.646G>A
NR_136160.2:n.738G>A
P00813:p.Gly216Arg

Protein change:

G216R; GLY216ARG

Links:

UniProtKB: P00813#VAR_002234; OMIM: 608958.0016; dbSNP: rs121908723

NCBI 1000 Genomes Browser:

rs121908723

Molecular consequence:

NM_001322051.2:c.607-109G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_000022.4:c.646G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001322050.2:c.241G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_136160.2:n.738G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

Clear Turn Off Turn On

Microbulbifer mangrovi strain DD-13 1210, whole genome shotgun sequence
Microbulbifer mangrovi strain DD-13 1210, whole genome shotgun sequence
gi|1151114168|ref|NZ_LZDE01000317.1 |WGS:NZ_LZDE01|1210

Nucleotide

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000321380	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Pathogenic (Jul 10, 2017)	germline	clinical testing	Citation Link,
SCV004704419	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Pathogenic (Mar 1, 2024)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000321380

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Pathogenic
(Jul 10, 2017)

germline

clinical testing

Citation Link,

SCV004704419

CeGaT Center for Human Genetics Tuebingen

criteria provided, single submitter

(CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)

Pathogenic
(Mar 1, 2024)

germline

clinical testing

Citation Link

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

Details of each submission

From GeneDx, SCV000321380.7

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

Description

The G216R missense variant in the ADA gene has been reported previously in association with adenosine adeaminase deficiency in patients of varied ancestries (Hirschhorn et al., 1991; Arredondo-Vega et al., 1998; Adams et al., 2015; Baffelli et al., 2015). It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. G216R is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. Missense variants in nearby residues (R211H/C, V213F, A215T, E217K) have been reported in the Human Gene Mutation Database in association with ADA-related disorders (Stenson et al., 2014), supporting the functional importance of this region of the protein. In addition, functional studies have shown that the G216R variant results in reduced catalytic activity and early clinical presentation of the disorder (Arredondo-Vega et al., 1998). Therefore, we consider this variant to be pathogenic.

#	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, SCV004704419.8

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

Description

ADA: PM3:Very Strong, PM2, PS3: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		1	not provided	not provided	not provided

Last Updated: Oct 20, 2024

ClinVar

Relating variation to medicine