Submissions for variant NM_001625.4(AK2):c.602A>T (p.Tyr201Phe)

gnomAD frequency: 0.00206  dbSNP: rs113711467

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001825004	SCV002074209	uncertain significance	not specified	2022-01-11	criteria provided, single submitter	clinical testing	Variant summary: AK2 c.602A>T (p.Tyr201Phe) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00022 in 246324 control chromosomes, predominantly at a frequency of 0.00034 within the Non-Finnish European subpopulation in the gnomAD database. This frequency is not significantly higher than expected for a pathogenic variant in AK2 causing Severe Combined Immunodeficiency (0.00022 vs 0.00035), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.602A>T in individuals affected with Severe Combined Immunodeficiency and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance.
Breakthrough Genomics, Breakthrough Genomics	RCV001573739	SCV005186599	uncertain significance	not provided		criteria provided, single submitter	not provided
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV001573739	SCV001800045	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001573739	SCV001975298	likely benign	not provided		no assertion criteria provided	clinical testing