Submissions for variant NM_001378183.1(PIEZO2):c.5257-1G>A

dbSNP: rs1555630216

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000578906	SCV000681212	pathogenic	not provided	2017-12-07	criteria provided, single submitter	clinical testing	The c.5083-1G>A variant in the PIEZO2 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This splice site variant destroys the canonical splice acceptor site in intron 35. It is predicted to cause abnormal gene splicing, either leading to an abnormal message that is subject to nonsense-mediated mRNA decay, or to an abnormal protein product if the message is used for protein translation. The c.5083-1G>A variant is not observed in large population cohorts (Lek et al., 2016). We interpret c.5083-1G>A as a pathogenic variant.
Undiagnosed Diseases Network, NIH	RCV000625965	SCV000746563	pathogenic	Arthrogryposis, distal, with impaired proprioception and touch	2017-12-11	criteria provided, single submitter	clinical testing	This splice site mutation is categorized as deleterious according to ACMG guidelines (PMID: 18414213) and was found in trans with another variant (c.1528-1G>A) in a 6-year-old female with ataxia, hypotonia, mild dysmorphic features, delayed motor development, scoliosis. It is predicted to cause abnormal gene splicing, either leading to an abnormal message that is subject to nonsense-mediated mRNA decay, or to an abnormal protein product if the message is used for protein translation.