ClinVar Miner

Submissions for variant NM_000022.4(ADA):c.239A>G (p.Lys80Arg)

gnomAD frequency: 0.05947  dbSNP: rs11555566
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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Severe Combined Immunodeficiency Variant Curation Expert Panel, ClinGen RCV000002031 SCV004242241 benign Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency 2024-01-23 reviewed by expert panel curation The NM_000022.4:c.239A>G variant in ADA is a missense variant predicted to cause substitution of lysine by arginine at amino acid 80 (p.Lys80Arg). The Popmax filtering allele frequency of this variant in the gnomAD v2.1.1 database is 0.06430, which is higher than the ClinGen SCID VCEP threshold (>0.00721) for BA1 (BA1). This variant has been observed in 551 homozygous individuals with no feature of SCID, a condition with full penetrance at an early age (BS2_Supporting). In summary, this variant meets the criteria to be classified as benign for SCID. ACMG/AMP criteria applied, as specified by the ClinGen SCID-VCEP: BA1 and BS2_Supporting. (VCEP specifications version 1).
Preventiongenetics, part of Exact Sciences RCV000247281 SCV000301544 benign not specified criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV000002031 SCV000434060 benign Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000247281 SCV000538233 benign not specified 2016-03-28 criteria provided, single submitter clinical testing Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Previously identified in SCID cell line in cis with L304R (Valerio 1986, PMID 3007108). However, a cell line with normal ADA activity was found to be homozygous for the L80R variant and functional assays suggested that the L304R variant was responsible for ADA inactivation. This variant has also been identified in unaffected individuals (Bell 2011 21228398).
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000247281 SCV001156714 benign not specified 2019-01-03 criteria provided, single submitter clinical testing
Invitae RCV000002031 SCV001730424 benign Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency 2024-02-01 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV000002031 SCV001738274 benign Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency 2021-06-10 criteria provided, single submitter clinical testing
GeneDx RCV001711065 SCV001944240 benign not provided 2015-03-03 criteria provided, single submitter clinical testing
OMIM RCV000002031 SCV000022189 uncertain significance Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency 2011-01-12 no assertion criteria provided literature only
Natera, Inc. RCV000002031 SCV001461850 benign Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency 2020-09-16 no assertion criteria provided clinical testing

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