Submissions for variant NM_001376.5(DYNC1H1):c.4515G>A (p.Ser1505=)

gnomAD frequency: 0.00016  dbSNP: rs186932188

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genetic Services Laboratory, University of Chicago	RCV000194555	SCV000247211	uncertain significance	not specified	2015-02-11	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000465307	SCV000385041	benign	Charcot-Marie-Tooth disease axonal type 2O	2018-01-13	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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Illumina Laboratory Services, Illumina	RCV000389663	SCV000385042	benign	Autosomal dominant cerebellar ataxia	2018-01-13	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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
GeneDx	RCV000194555	SCV000512896	benign	not specified	2015-08-26	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000465307	SCV000559772	benign	Charcot-Marie-Tooth disease axonal type 2O	2024-01-20	criteria provided, single submitter	clinical testing
Molecular Genetics Laboratory, London Health Sciences Centre	RCV001172865	SCV001335938	likely benign	Charcot-Marie-Tooth disease		criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV002262783	SCV002545206	likely benign	not provided	2024-06-01	criteria provided, single submitter	clinical testing	DYNC1H1: BP4, BP7
Ambry Genetics	RCV002336510	SCV002635149	likely benign	Inborn genetic diseases	2018-01-24	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, 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.