Submissions for variant NM_002180.3(IGHMBP2):c.2362C>T (p.Arg788Ter)

gnomAD frequency: 0.00001  dbSNP: rs199839840

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
CeGaT Center for Human Genetics Tuebingen	RCV001310976	SCV001500981	pathogenic	not provided	2020-11-01	criteria provided, single submitter	clinical testing
Invitae	RCV001869220	SCV002217170	pathogenic	Autosomal recessive distal spinal muscular atrophy 1; Charcot-Marie-Tooth disease axonal type 2S	2024-01-05	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg788*) in the IGHMBP2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in IGHMBP2 are known to be pathogenic (PMID: 14681881, 25439726, 25568292). This variant is present in population databases (rs199839840, gnomAD 0.01%). This premature translational stop signal has been observed in individual(s) with spinal muscular atrophy with respiratory distress type 1 (PMID: 14681881, 20859832, 23449687, 29761130). ClinVar contains an entry for this variant (Variation ID: 637262). For these reasons, this variant has been classified as Pathogenic.
Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein	RCV002252236	SCV002523243	likely pathogenic	See cases	2019-09-17	criteria provided, single submitter	clinical testing	ACMG classification criteria: PVS1, PM2
GeneDx	RCV001310976	SCV002577193	pathogenic	not provided	2022-09-29	criteria provided, single submitter	clinical testing	Identified in the presence of a second IGHMBP2 variant, phase unknown, in patients with clinical features consistent with SMARD1 in the published literature (Grohmann et al., 2003; Chiu et al., 2018); Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 21827898, 15248100, 26354092, 20859832, 25525159, 14681881, 32028661, 29761130)
Revvity Omics, Revvity	RCV001310976	SCV003818321	pathogenic	not provided	2022-11-22	criteria provided, single submitter	clinical testing
Inherited Neuropathy Consortium	RCV000789336	SCV000928689	uncertain significance	Neuronopathy, distal hereditary motor, autosomal dominant		no assertion criteria provided	literature only
Genesis Genome Database	RCV000856977	SCV000999544	uncertain significance	Charcot-Marie-Tooth disease	2019-08-14	no assertion criteria provided	research
Biochemical Molecular Genetic Laboratory, King Abdulaziz Medical City	RCV000985181	SCV001133196	likely pathogenic	Autosomal recessive distal spinal muscular atrophy 1	2019-09-26	no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV001310976	SCV001917089	pathogenic	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001310976	SCV001959864	pathogenic	not provided		no assertion criteria provided	clinical testing