Submissions for variant NM_004408.4(DNM1):c.849+6C>T

gnomAD frequency: 0.00013  dbSNP: rs527412689

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV001698249	SCV000531416	benign	not provided	2020-01-27	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000442593	SCV000594384	uncertain significance	not specified	2017-02-20	criteria provided, single submitter	clinical testing
Invitae	RCV000703832	SCV000832754	benign	Developmental and epileptic encephalopathy, 31	2023-12-21	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002522487	SCV003737687	likely benign	Inborn genetic diseases	2022-05-31	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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000442593	SCV004020973	uncertain significance	not specified	2023-06-28	criteria provided, single submitter	clinical testing	Variant summary: DNM1 c.849+6C>T alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. Although four computational tools predict the variant preserves the nearby canonical 5' splice donor site, two also predict the variant creates a cryptic 5' donor site 4nt downstream into intron 6. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00012 in 250320 control chromosomes (gnomAD). To our knowledge, no occurrence of c.849+6C>T in individuals affected with Developmental And Epileptic Encephalopathy, 31 and no experimental evidence demonstrating its impact on protein function have been reported. Four ClinVar submitters have assessed the variant since 2014: one classified the variant as uncertain significance, one as likely benign, and two as benign. Based on the evidence outlined above, the variant was classified as uncertain significance.
PreventionGenetics, part of Exact Sciences	RCV003932666	SCV004752096	likely benign	DNM1-related condition	2019-07-03	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).