Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000201941 | SCV000936697 | pathogenic | Spinal muscular atrophy, distal, autosomal recessive, 5 | 2019-07-31 | criteria provided, single submitter | clinical testing | This sequence change affects a donor splice site in intron 5 of the DNAJB2 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is present in population databases (rs756614404, ExAC 0.002%). This variant has been reported in the homozygous state in multiple individuals affected with distal hereditary motor neuropathy (dHMN) or Charcot-Marie-Tooth (CMT) and has been observed to segregate with disease in several families (PMID: 22522442, 27083531). ClinVar contains an entry for this variant (Variation ID: 217886). Experimental studies have shown that this splicing variant results in the retention of full or partial intron 5 sequence and the abnormal transcripts contain premature termination codons. In addition, DNAJB2 protein expression was significantly reduced in fibroblasts derived from affected individuals (PMID: 22522442). For these reasons, this variant has been classified as Pathogenic. |
Mendelics | RCV000201941 | SCV000256882 | pathogenic | Spinal muscular atrophy, distal, autosomal recessive, 5 | 2014-08-08 | no assertion criteria provided | clinical testing | |
Inherited Neuropathy Consortium | RCV000789088 | SCV000928437 | uncertain significance | Charcot-Marie-Tooth disease | no assertion criteria provided | literature only |