NM_000022.4(ADA):c.320T>C (p.Leu107Pro) AND Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency

Germline classification:: Pathogenic/Likely pathogenic (8 submissions)
Last evaluated:: Jan 16, 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:: RCV000002042.28

Allele description [Variation Report for NM_000022.4(ADA):c.320T>C (p.Leu107Pro)]

NM_000022.4(ADA):c.320T>C (p.Leu107Pro)

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.320T>C (p.Leu107Pro)

HGVS:

NC_000020.11:g.44626498A>G
NG_007385.1:g.30238T>C
NM_000022.4:c.320T>CMANE SELECT
NM_001322050.2:c.31T>C
NM_001322051.2:c.320T>C
NP_000013.2:p.Leu107Pro
NP_001308979.1:p.Trp11Arg
NP_001308980.1:p.Leu107Pro
LRG_16t1:c.320T>C
LRG_16:g.30238T>C
NC_000020.10:g.43255139A>G
NM_000022.2:c.320T>C
NM_000022.3:c.320T>C
NR_136160.2:n.412T>C
P00813:p.Leu107Pro

Protein change:

L107P; LEU107PRO

Links:

UniProtKB: P00813#VAR_002219; UniProtKB/Swiss-Prot: VAR_002219; OMIM: 608958.0013; dbSNP: rs121908739

NCBI 1000 Genomes Browser:

rs121908739

Molecular consequence:

NM_000022.4:c.320T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001322050.2:c.31T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001322051.2:c.320T>C - missense variant - [Sequence Ontology: SO:0001583]
NR_136160.2:n.412T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency
Synonyms:: ADA-SCID; SCID DUE TO ADA DEFICIENCY, EARLY-ONSET; ADA deficiency; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0007064; MedGen: C1863236; Orphanet: 277; OMIM: 102700

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
SCV000022200	OMIM	no assertion criteria provided	Pathogenic (Aug 1, 1990)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV000090622	UniProtKB/Swiss-Prot	no classification provided	not provided	unknown	not provided	PubMed (1) [See all records that cite this PMID]
SCV000644840	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 16, 2024)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 2166947, 2758612, 9225964, 7599635, 9361033, 9758612, 28492532
SCV000795157	Counsyl	no assertion criteria provided	Likely pathogenic (Oct 27, 2017)	unknown	clinical testing	PubMed (5) [See all records that cite these PMIDs] 2166947, 9758612, 7599635, 9361033, 27129325
SCV000894219	Fulgent Genetics, Fulgent Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Mar 31, 2022)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001461849	Natera, Inc.	no assertion criteria provided	Pathogenic (Sep 16, 2020)	germline	clinical testing
SCV001977519	Genome-Nilou Lab	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Aug 10, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004211627	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Sep 1, 2023)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

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
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	no	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	not provided	not provided	not provided	not provided	1	not provided	literature only
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

Rhabdomyolysis in a case of free-base cocaine ("crack") overdose.

Jandreski MA, Bermes EW, Leischner R, Kahn SE.

Clin Chem. 1989 Jul;35(7):1547-9.

PubMed [citation]

PMID:: 2758612

Two newly identified mutations (Thr233Ile and Leu152Met) in partially adenosine deaminase-deficient (ADA-) individuals that result in differing biochemical and metabolic phenotypes.

Hirschhorn R, Borkowsky W, Jiang CK, Yang DR, Jenkins T.

Hum Genet. 1997 Jul;100(1):22-9.

PubMed [citation]

PMID:: 9225964

See all PubMed Citations (9)

PMC

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.

Genetics in medicine : official journal of the American College of Medical Genetics. 2015 Mar 5; 17(5): 405-424

PMC [article]

PMCID:: PMC4544753
PMID:: 25741868
DOI:: 10.1038/gim.2015.30

Details of each submission

From OMIM, SCV000022200.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

In 2 unrelated patients with SCID due to ADA deficiency (102700), Hirschhorn et al. (1990) identified a 320T-C transition in exon 4 of the ADA gene, resulting in a leu107-to-pro (L107P) substitution. Analysis of enzyme activity showed that the L107P mutation is a null allele.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From UniProtKB/Swiss-Prot, SCV000090622.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	not provided	1	not provided	not provided		not provided	not provided	not provided	not provided

From Invitae, SCV000644840.7

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (7)

Description

This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 107 of the ADA protein (p.Leu107Pro). This variant is present in population databases (rs121908739, gnomAD 0.03%). This missense change has been observed in individual(s) with adenosine deaminase deficiency (PMID: 2166947, 2758612, 7599635, 9225964). ClinVar contains an entry for this variant (Variation ID: 1965). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on ADA protein function. Experimental studies have shown that this missense change affects ADA function (PMID: 7599635, 9361033, 9758612). For these reasons, this variant has been 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

From Counsyl, SCV000795157.2

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

#	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 Fulgent Genetics, Fulgent Genetics, SCV000894219.2

#	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	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Natera, Inc., SCV001461849.1

#	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	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Genome-Nilou Lab, SCV001977519.1

#	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	no	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Baylor Genetics, SCV004211627.1

#	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	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Apr 20, 2024

Relating variation to medicine