Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
UW Hindbrain Malformation Research Program, |
RCV000201630 | SCV000256527 | likely pathogenic | Joubert syndrome 6 | 2015-02-23 | criteria provided, single submitter | research | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV005055723 | SCV005726152 | likely pathogenic | Joubert syndrome and related disorders | 2024-11-20 | criteria provided, single submitter | clinical testing | Variant summary: TMEM67 c.2322+5delG alters a conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. Several computational tools predict a significant impact on normal splicing: Four predict the variant abolishes a 5' splicing donor site. At least one publication reports experimental evidence that this variant affects mRNA splicing, resulting in the skipping of exon 22 (Tsurusaki_2013). The variant allele was found at a frequency of 4e-06 in 251096 control chromosomes. c.2322+5delG has been reported in the literature in individuals affected with Joubert Syndrome And Related Disorders (e.g. Tsurusaki_2013, Bachmann-Gagescu_JMG_2015). The following publications have been ascertained in the context of this evaluation (PMID: 26092869, 23034536). ClinVar contains an entry for this variant (Variation ID: 217731). Based on the evidence outlined above, the variant was classified as likely pathogenic. |