NM_000022.4(ADA):c.872C>T (p.Ser291Leu) AND Severe combined immunodeficiency disease

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Aug 6, 2024
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV004766976.1

Allele description [Variation Report for NM_000022.4(ADA):c.872C>T (p.Ser291Leu)]

NM_000022.4(ADA):c.872C>T (p.Ser291Leu)

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.872C>T (p.Ser291Leu)

HGVS:

NC_000020.11:g.44621121G>A
NG_007385.1:g.35615C>T
NM_000022.4:c.872C>TMANE SELECT
NM_001322050.2:c.467C>T
NM_001322051.2:c.800C>T
NP_000013.2:p.Ser291Leu
NP_001308979.1:p.Ser156Leu
NP_001308980.1:p.Ser267Leu
LRG_16t1:c.872C>T
LRG_16:g.35615C>T
NC_000020.10:g.43249762G>A
NM_000022.2:c.872C>T
NM_000022.3:c.872C>T
NR_136160.2:n.899C>T
P00813:p.Ser291Leu

Protein change:

S156L; SER291LEU

Links:

UniProtKB: P00813#VAR_002237; UniProtKB/Swiss-Prot: VAR_002237; OMIM: 608958.0019; dbSNP: rs121908721

NCBI 1000 Genomes Browser:

rs121908721

Molecular consequence:

NM_000022.4:c.872C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001322050.2:c.467C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001322051.2:c.800C>T - missense variant - [Sequence Ontology: SO:0001583]
NR_136160.2:n.899C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Severe combined immunodeficiency disease (SCID)
Synonyms:: Severe combined immunodeficiency; Severe Combined Immune Deficiency
Identifiers:: MONDO: MONDO:0015974; MeSH: D016511; MedGen: C0085110; Human Phenotype Ontology: HP:0004430

Recent activity

Clear Turn Off Turn On

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
SCV005381321	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Pathogenic (Aug 6, 2024)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 9758612, 1401934, 19179314, 26255240, 26376800 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV005381321

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Pathogenic
(Aug 6, 2024)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

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

Citations

PubMed

Adenosine deaminase deficiency: genotype-phenotype correlations based on expressed activity of 29 mutant alleles.

Arredondo-Vega FX, Santisteban I, Daniels S, Toutain S, Hershfield MS.

Am J Hum Genet. 1998 Oct;63(4):1049-59.

PubMed [citation]

PMID:: 9758612
PMCID:: PMC1377486

Novel deletion and a new missense mutation (Glu 217 Lys) at the catalytic site in two adenosine deaminase alleles of a patient with neonatal onset adenosine deaminase- severe combined immunodeficiency.

Hirschhorn R, Nicknam MN, Eng F, Yang DR, Borkowsky W.

J Immunol. 1992 Nov 1;149(9):3107-12.

PubMed [citation]

PMID:: 1401934

See all PubMed Citations (5)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV005381321.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

Variant summary: ADA c.872C>T (p.Ser291Leu) results in a non-conservative amino acid change located in the Adenosine deaminase domain (IPR001365) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2.4e-05 in 251496 control chromosomes. c.872C>T has been reported in the literature in individuals affected with Severe Combined Immunodeficiency (Hirschhorn_1992, Aiuti_2009, Adams_2015, Baffelli_2015). These data indicate that the variant is likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in <10% of normal activity (Arredondo-Vega_1998). The following publications have been ascertained in the context of this evaluation (PMID: 1401934, 26255240, 19179314, 9758612, 26376800). ClinVar contains an entry for this variant (Variation ID: 1971). Based on the evidence outlined above, the variant was classified as pathogenic.

#	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

Last Updated: May 16, 2025

ClinVar

Relating variation to medicine