Submissions for variant NM_004738.5(VAPB):c.510G>A (p.Met170Ile)

gnomAD frequency: 0.00170  dbSNP: rs143144050

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV002254554	SCV000641274	likely benign	Amyotrophic lateral sclerosis type 8; Adult-onset proximal spinal muscular atrophy, autosomal dominant	2024-01-30	criteria provided, single submitter	clinical testing
GeneDx	RCV001579802	SCV000731031	benign	not provided	2021-01-25	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 22878164, 23971766, 25382069, 28430856)
Mendelics	RCV000990320	SCV001141260	likely benign	Amyotrophic lateral sclerosis type 8	2019-05-28	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001143187	SCV001303692	benign	Adult-onset proximal spinal muscular atrophy, autosomal dominant	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign.
Illumina Laboratory Services, Illumina	RCV000990320	SCV001303693	benign	Amyotrophic lateral sclerosis type 8	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign.
CeGaT Center for Human Genetics Tuebingen	RCV001579802	SCV002585890	benign	not provided	2022-08-01	criteria provided, single submitter	clinical testing	VAPB: BP4, BS1, BS2
Ambry Genetics	RCV002341333	SCV002642550	likely benign	Inborn genetic diseases	2019-11-08	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
PreventionGenetics, part of Exact Sciences	RCV003915562	SCV004735680	likely benign	VAPB-related condition	2019-04-12	criteria provided, single submitter	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).
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV001579802	SCV001808567	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV001579802	SCV001925134	likely benign	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV001579802	SCV001930025	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001579802	SCV001973123	likely benign	not provided		no assertion criteria provided	clinical testing