Submissions for variant NM_001005361.3(DNM2):c.2576_2581del (p.Thr859_Ile860del)

dbSNP: rs876661117

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000422170	SCV000279572	uncertain significance	not provided	2019-07-01	criteria provided, single submitter	clinical testing	Previously reported in the heterozygous state, in a different transcript (NM_004945) with the alternate nomenclature, p.T855_I856del, in a 67 year old individual with infantile onset distal lower limb muscle weakness and atrophy, gait difficulties, lower limb cramps and bilateral foot drop with family history of a similarly affected sibling and parent (Claeys et al., 2009).; In-frame deletion of 2 amino acids in a non-repeat region; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 19502294)
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	RCV000422170	SCV000511354	uncertain significance	not provided	2016-11-22	criteria provided, single submitter	clinical testing	Converted during submission to Uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001216040	SCV001387812	uncertain significance	Charcot-Marie-Tooth disease dominant intermediate B	2023-04-26	criteria provided, single submitter	clinical testing	In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 234609). This variant is also known as c.2564_2569delCCATTA, Thr855_Ile856del. This variant has been observed in individual(s) with Charcot-Marie-Tooth disease (PMID: 19502294). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant, c.2576_2581del, results in the deletion of 2 amino acid(s) of the DNM2 protein (p.Thr859_Ile860del), but otherwise preserves the integrity of the reading frame.
Revvity Omics, Revvity	RCV000422170	SCV003830477	uncertain significance	not provided	2022-11-29	criteria provided, single submitter	clinical testing