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NM_000022.4(ADA):c.479-2del AND Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Dec 27, 2018
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:
RCV000809597.5

Allele description [Variation Report for NM_000022.4(ADA):c.479-2del]

NM_000022.4(ADA):c.479-2del

Gene:
ADA:adenosine deaminase [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
20q13.12
Genomic location:
Preferred name:
NM_000022.4(ADA):c.479-2del
HGVS:
  • NC_000020.11:g.44624331del
  • NG_007385.1:g.32405del
  • NM_000022.4:c.479-2delMANE SELECT
  • NM_001322050.2:c.74-2del
  • NM_001322051.2:c.479-2del
  • LRG_16t1:c.479-2del
  • LRG_16:g.32405del
  • NC_000020.10:g.43252972del
  • NM_000022.2:c.479-2del
Links:
dbSNP: rs1600921786
NCBI 1000 Genomes Browser:
rs1600921786
Molecular consequence:
  • NM_000022.4:c.479-2del - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001322050.2:c.74-2del - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001322051.2:c.479-2del - splice acceptor variant - [Sequence Ontology: SO:0001574]

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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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000949755Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Likely pathogenic
(Dec 27, 2018) 		germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]
PMID:
16199547
PMCID:
PMC1735933

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
See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000949755.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in ADA are known to be pathogenic (PMID: 26255240, 26376800). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has not been reported in the literature in individuals with ADA-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change affects an acceptor splice site in intron 5 of the ADA gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024