Submissions for variant NM_001376.5(DYNC1H1):c.7431C>T (p.Pro2477=)

gnomAD frequency: 0.00004  dbSNP: rs375687099

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV001111364	SCV001268914	uncertain significance	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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Illumina Laboratory Services, Illumina	RCV001113373	SCV001271138	uncertain significance	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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Molecular Genetics Laboratory, London Health Sciences Centre	RCV001173178	SCV001336258	likely benign	Charcot-Marie-Tooth disease		criteria provided, single submitter	clinical testing
Invitae	RCV001111364	SCV002373306	likely benign	Charcot-Marie-Tooth disease axonal type 2O	2023-12-19	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003906209	SCV004725692	likely benign	DYNC1H1-related condition	2019-06-12	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).