Submissions for variant NM_001383.6(DPH1):c.919C>T (p.Arg307Ter)

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV004703122	SCV005202911	pathogenic	Developmental delay with short stature, dysmorphic facial features, and sparse hair 1	2024-07-23	criteria provided, single submitter	clinical testing	Variant summary: DPH1 c.919C>T (p.Arg307X; also known as R312* in the literature) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant allele was found at a frequency of 4e-06 in 249522 control chromosomes (gnomAD). To our knowledge, no occurrence of c.919C>T in individuals affected with developmental delay with short Stature, dysmorphic facial features, and sparse hair 1 has been reported. At least one publication reports experimental evidence evaluating an impact on protein function, however, does not allow convincing conclusions about the variant effect (Mayer_2017). The following publication has been ascertained in the context of this evaluation (PMID: 28245596). No submitters have cited clinical-significance assessments for this variant to ClinVar. Based on the evidence outlined above, the variant was classified as pathogenic.