NM_000022.4(ADA):c.1009G>T (p.Glu337Ter) AND Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Aug 25, 2022
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:: RCV002755400.2

Allele description [Variation Report for NM_000022.4(ADA):c.1009G>T (p.Glu337Ter)]

NM_000022.4(ADA):c.1009G>T (p.Glu337Ter)

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.1009G>T (p.Glu337Ter)

HGVS:

NC_000020.11:g.44620368C>A
NG_007385.1:g.36368G>T
NM_000022.4:c.1009G>TMANE SELECT
NM_001322050.2:c.604G>T
NM_001322051.2:c.937G>T
NP_000013.2:p.Glu337Ter
NP_000013.2:p.Glu337Ter
NP_001308979.1:p.Glu202Ter
NP_001308980.1:p.Glu313Ter
LRG_16t1:c.1009G>T
LRG_16:g.36368G>T
LRG_16p1:p.Glu337Ter
NC_000020.10:g.43249009C>A
NM_000022.2:c.1009G>T
NR_136160.2:n.1036G>T

Protein change:

E202*

Molecular consequence:

NR_136160.2:n.1036G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_000022.4:c.1009G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322050.2:c.604G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322051.2:c.937G>T - nonsense - [Sequence Ontology: SO:0001587]

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003011112	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 25, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 26255240, 26376800, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003011112

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Aug 25, 2022)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

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

Spectrum of mutations in a cohort of UK patients with ADA deficient SCID: Segregation of genotypes with specific ethnicities.

Adams SP, Wilson M, Harb E, Fairbanks L, Xu-Bayford J, Brown L, Kearney L, Madkaikar M, Bobby Gaspar H.

Clin Immunol. 2015 Dec;161(2):174-9. doi: 10.1016/j.clim.2015.08.001. Epub 2015 Aug 5.

PubMed [citation]

PMID:: 26255240

Diagnosis, Treatment and Long-Term Follow Up of Patients with ADA Deficiency: a Single-Center Experience.

Baffelli R, Notarangelo LD, Imberti L, Hershfield MS, Serana F, Santisteban I, Bolda F, Porta F, Lanfranchi A.

J Clin Immunol. 2015 Oct;35(7):624-37. doi: 10.1007/s10875-015-0191-z. Epub 2015 Sep 16.

PubMed [citation]

PMID:: 26376800

See all PubMed Citations (3)

Details of each submission

From Invitae, SCV003011112.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

For these reasons, this variant has been classified as Pathogenic. This premature translational stop signal has been observed in individual(s) with adenosine deaminase deficiency (PMID: 26376800). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Glu337*) in the ADA gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ADA are known to be pathogenic (PMID: 26255240, 26376800).

#	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: Feb 20, 2024

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