Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
New York Genome Center | RCV002266698 | SCV002548769 | likely pathogenic | Hypomagnesemia, seizures, and intellectual disability 1 | 2021-09-08 | criteria provided, single submitter | clinical testing | The c.522dup (p.(Ile175AspfsTer236)) frameshift variant in CNNM2 has not previously been reported in the literature or public variant repositories (ClinVar and LOVD), and it has not been observed in the population databases (gnomAD v2.1 and v3, TOPMed Freeze 5). This variant occurs in the first exon of this 8-exon gene; however, it is expected to subject to nonsense mediated decay or result in disruption of the reading frame either by a protein truncation or loss of N-terminal part of the protein. There are other missense and frameshift variants upstream of the c.522dup variant reported as likely pathogenic and pathogenic in the literature [PMID:21397062,24699222] and ClinVar [ClinVar ID= 817123, 996041]. Based on the available evidence this c.522dup variant in CNNM2 is classified as Likely pathogenic. |