Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| ARUP Laboratories, |
RCV000507416 | SCV000603857 | pathogenic | not specified | 2016-11-02 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001731315 | SCV001983288 | pathogenic | not provided | 2023-11-10 | criteria provided, single submitter | clinical testing | Canonical splice site variant predicted to result in a null allele in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 22578326, 27312216, 36147510) |
| Division Of Personalized Genomic Medicine, |
RCV000029166 | SCV004190165 | pathogenic | Chudley-McCullough syndrome | 2021-12-13 | criteria provided, single submitter | clinical testing | The c.1062+1G>T variant in the GPSM2 gene is a heterozygous canonical splice site variant, which affects an acceptor splice site in intron 9 (14 introns total; NM_013296.5). This mutation results in loss of exon 9 in the transcript and is predicted to generate a truncated protein, p.Arg318Argfs*8 (PMID: 22578326). Homozygous or compound heterozygous loss-of-function variants in GPSM2 have been reported in patient cohorts with Chudley-McCullough syndrome (PMID: 22578326). This variant in a homozygous state has been reported in two families with autosomal recessive Chudley-McCullough syndrome (PMID: 22578326 and 27312216). This variant has not been observed in the Genome Aggregation Database (gnomAD), indicating it is not a common benign variant in the populations represented in this database. This variant has been reported in the ClinVar database as a pathogenic variant (Variant ID: 35494; last accessed 12/13/2021). |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000029166 | SCV005395818 | pathogenic | Chudley-McCullough syndrome | 2024-09-17 | criteria provided, single submitter | clinical testing | Variant summary: GPSM2 c.1062+1G>T is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing and loss of GPSM2 function. 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 9 (Doherty_2012). The variant allele was found at a frequency of 8e-06 in 249976 control chromosomes. c.1062+1G>T has been reported in the literature in individuals affected with Chudley-McCullough Syndrome (e.g. Doherty_2012, Carlson_2023). These data indicate that the variant is very likely to be associated with disease. The following publications have been ascertained in the context of this evaluation (PMID: 22578326, 36633841). ClinVar contains an entry for this variant (Variation ID: 35494). Based on the evidence outlined above, the variant was classified as pathogenic. |
| OMIM | RCV000029166 | SCV000051811 | pathogenic | Chudley-McCullough syndrome | 2012-06-08 | no assertion criteria provided | literature only |