Submissions for variant NM_001005361.3(DNM2):c.958G>A (p.Asp320Asn)

gnomAD frequency: 0.00023  dbSNP: rs150613209

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genetic Services Laboratory, University of Chicago	RCV000145921	SCV000193058	benign	not specified	2013-02-08	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000280887	SCV000410357	benign	Autosomal dominant centronuclear myopathy	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 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	RCV000802315	SCV000410358	benign	Charcot-Marie-Tooth disease dominant intermediate B	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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
GeneDx	RCV000145921	SCV000726425	likely benign	not specified	2018-01-16	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.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000756033	SCV000883738	uncertain significance	not provided	2017-06-14	criteria provided, single submitter	clinical testing	The p.Asp320Asn variant (rs150613209) has not been reported in the medical literature, nor has it been previously identified in our laboratory; however, it is listed in the ClinVar database (Variation ID: 158529). This variant is listed in the Genome Aggregation Database (gnomAD) browser with an overall frequency of 0.01% (identified in 33 out of 276,996 chromosomes). The aspartic acid at codon 320 is moderately conserved considering 14 species (Alamut software v2.9), and computational analyses return mixed results regarding the effect of this variant on DNM2 protein structure/function (SIFT: tolerated, PolyPhen2: benign, and Mutation Taster: disease causing). Therefore, based on the available information, the clinical significance of the p.Asp320Asn variant cannot be determined with certainty.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000802315	SCV000942140	likely benign	Charcot-Marie-Tooth disease dominant intermediate B	2024-11-29	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002512574	SCV003693776	likely benign	Inborn genetic diseases	2022-10-26	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.
Revvity Omics, Revvity	RCV000756033	SCV003830503	uncertain significance	not provided	2024-01-18	criteria provided, single submitter	clinical testing