Submissions for variant NM_025132.4(WDR19):c.3823C>G (p.Pro1275Ala)

gnomAD frequency: 0.00027  dbSNP: rs200670161

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001064835	SCV001229761	uncertain significance	Asphyxiating thoracic dystrophy 5; Senior-Loken syndrome 8	2022-10-04	criteria provided, single submitter	clinical testing	This sequence change replaces proline, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 1275 of the WDR19 protein (p.Pro1275Ala). This variant is present in population databases (rs200670161, gnomAD 0.05%). This variant has not been reported in the literature in individuals affected with WDR19-related conditions. ClinVar contains an entry for this variant (Variation ID: 858859). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
AiLife Diagnostics, AiLife Diagnostics	RCV001700692	SCV002502607	uncertain significance	not provided	2022-03-24	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV002479381	SCV002781128	uncertain significance	Asphyxiating thoracic dystrophy 5; Nephronophthisis 13; Cranioectodermal dysplasia 4; Senior-Loken syndrome 8; Spermatogenic failure 72	2022-02-03	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002555835	SCV003583223	uncertain significance	Inborn genetic diseases	2021-10-18	criteria provided, single submitter	clinical testing	The c.3823C>G (p.P1275A) alteration is located in exon 34 (coding exon 34) of the WDR19 gene. This alteration results from a C to G substitution at nucleotide position 3823, causing the proline (P) at amino acid position 1275 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Clinical Genetics, Academic Medical Center	RCV001700692	SCV001917555	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001700692	SCV001964983	uncertain significance	not provided		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV001700692	SCV002037083	uncertain significance	not provided		no assertion criteria provided	clinical testing