Submissions for variant NM_001376.5(DYNC1H1):c.13707G>A (p.Thr4569=)

gnomAD frequency: 0.00023  dbSNP: rs138571942

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001078503	SCV000287108	benign	Charcot-Marie-Tooth disease axonal type 2O	2024-01-25	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001078503	SCV000385224	likely 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 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	RCV000264240	SCV000385226	likely 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
GeneDx	RCV000757191	SCV000518872	benign	not provided	2020-06-25	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000757191	SCV000885329	likely benign	not provided	2017-05-26	criteria provided, single submitter	clinical testing	The c.13707G>A variant (rs138571942) does not alter the amino acid sequence of the DYNC1H1 protein and computational splice site prediction algorithms do not predict a change in the nearest splice site or creation of a cryptic splice site. This variant has not been reported in association with hereditary neuropathy in medical literature or in gene specific variation databases. This variant is listed in the Exome Aggregation Consortium Browser with an overall population frequency of 0.047 percent (identified on 57 out of 121,390 chromosomes). Based on these observations, the c.13707G>A variant is likely to be benign.
Molecular Genetics Laboratory, London Health Sciences Centre	RCV001174060	SCV001337180	likely benign	Charcot-Marie-Tooth disease		criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002378982	SCV002701213	likely benign	Inborn genetic diseases	2018-11-26	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.
CeGaT Center for Human Genetics Tuebingen	RCV000757191	SCV005093786	likely benign	not provided	2024-07-01	criteria provided, single submitter	clinical testing	DYNC1H1: BP4, BP7