Submissions for variant NM_005797.4(MPZL2):c.463del (p.Ala155fs)

dbSNP: rs759432278

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
3billion	RCV000850011	SCV002059095	pathogenic	Hearing loss, autosomal recessive 111	2022-01-03	criteria provided, single submitter	clinical testing	Frameshift: predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant (PVS1_VS). It is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.00003, PM2_M). The variant has been reported to be associated with MPZL2 related disorder (ClinVar ID: VCV000689320, PMID:32203226, 3billion dataset). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline.
Genetic Testing Center for Deafness, Department of Otolaryngology Head & Neck Surgery, Institute of Otolaryngology, Chinese PLA General Hospital	RCV000850011	SCV002762663	pathogenic	Hearing loss, autosomal recessive 111	2022-12-13	criteria provided, single submitter	clinical testing
Laboratory of Molecular Genetics, Brain Korea 21 PLUS Project for Medical Sciences, Yonsei University College of Medicine	RCV000850011	SCV000986687	pathogenic	Hearing loss, autosomal recessive 111	2019-08-28	no assertion criteria provided	research	Individual with NSHL carried compound heterozygous variants in MPZL2. AR NSHL had a characteristic of moderate and progressive hearing loss. Hearing impairment in the individual was a sporadic case in his family.