Submissions for variant NM_001104631.2(PDE4D):c.125C>A (p.Pro42Gln)

gnomAD frequency: 0.00013  dbSNP: rs372946517

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000388985	SCV000458007	benign	Acrodysostosis 2 with or without hormone resistance	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000903518	SCV001047990	benign	not provided	2024-01-30	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002523528	SCV003645430	uncertain significance	Inborn genetic diseases	2021-07-23	criteria provided, single submitter	clinical testing	The c.125C>A (p.P42Q) alteration is located in exon 1 (coding exon 1) of the PDE4D gene. This alteration results from a C to A substitution at nucleotide position 125, causing the proline (P) at amino acid position 42 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
GeneDx	RCV000903518	SCV004028013	uncertain significance	not provided	2023-02-20	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
PreventionGenetics, part of Exact Sciences	RCV003932456	SCV004755247	likely benign	PDE4D-related disorder	2023-12-20	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).