Submissions for variant NM_001376.5(DYNC1H1):c.10941G>A (p.Pro3647=)

gnomAD frequency: 0.00004  dbSNP: rs374214760

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000609342	SCV000726154	likely benign	not specified	2017-12-27	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae	RCV000797989	SCV000937581	likely benign	Charcot-Marie-Tooth disease axonal type 2O	2024-01-09	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000797989	SCV001272888	likely benign	Charcot-Marie-Tooth disease axonal type 2O	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Illumina Laboratory Services, Illumina	RCV001114964	SCV001272889	likely benign	Autosomal dominant cerebellar ataxia	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Molecular Genetics Laboratory, London Health Sciences Centre	RCV001173874	SCV001336990	likely benign	Charcot-Marie-Tooth disease		criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001811106	SCV001477782	likely benign	not provided	2020-04-13	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002448889	SCV002735645	likely benign	Inborn genetic diseases	2017-10-27	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.
CeGaT Center for Human Genetics Tuebingen	RCV001811106	SCV004135187	likely benign	not provided	2023-04-01	criteria provided, single submitter	clinical testing	DYNC1H1: BP4, BP7
PreventionGenetics, part of Exact Sciences	RCV003892364	SCV004709487	likely benign	DYNC1H1-related condition	2021-09-09	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).