Submissions for variant NM_000215.4(JAK3):c.1142+13C>A

dbSNP: rs3212733

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000125440	SCV000168892	benign	not specified	2013-06-06	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Illumina Laboratory Services, Illumina	RCV000296653	SCV000411121	benign	T-B+ severe combined immunodeficiency due to JAK3 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000125440	SCV000919545	benign	not specified	2017-11-22	criteria provided, single submitter	clinical testing	Variant summary: The JAK3 c.1142+13C>A variant involves the alteration of a non-conserved nucleotide. One in silico tool predicts a benign outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. ESE finder predicts that this variant may affect ESE site of SC35 and SF2/ASF, however, these predictions have yet to be confirmed by functional studies. This variant was found in 28270/175038 control chromosomes (2599 homozygotes) at a frequency of 0.1615078, which is approximately 150 times the estimated maximal expected allele frequency of a pathogenic JAK3 variant (0.0010801), suggesting this variant is likely a benign polymorphism. This variant has also been reported via publications as a polymorphism (Schumacher 2000, Notarangelo 2001). In addition, multiple clinical diagnostic laboratories classified this variant as benign. Taken together, this variant is classified as benign.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000296653	SCV001730615	benign	T-B+ severe combined immunodeficiency due to JAK3 deficiency	2024-02-01	criteria provided, single submitter	clinical testing
Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	RCV000125440	SCV004233931	benign	not specified	2024-01-24	criteria provided, single submitter	clinical testing	This variant is classified as Benign based on local population frequency. This variant was detected in 43% of patients studied by a panel of primary immunodeficiencies. Number of patients: 38. Only high quality variants are reported.
Breakthrough Genomics, Breakthrough Genomics	RCV004717025	SCV005313621	benign	not provided		criteria provided, single submitter	not provided