Total submissions: 8
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001043665 | SCV001207423 | pathogenic | Autosomal recessive limb-girdle muscular dystrophy type 2O; Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B3 | 2024-01-04 | criteria provided, single submitter | clinical testing | This sequence change affects a donor splice site in intron 21 of the POMGNT1 gene. While this variant is not anticipated to result in nonsense mediated decay, it likely alters RNA splicing and results in a disrupted protein product. 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. Disruption of this splice site has been observed in individuals with muscle-eye-brain disease (PMID: 15466003, 22554691, 28424332). ClinVar contains an entry for this variant (Variation ID: 56592). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |
Myriad Genetics, |
RCV001810415 | SCV002060143 | pathogenic | Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A3 | 2021-11-16 | criteria provided, single submitter | clinical testing | NM_017739.3(POMGNT1):c.1895+1G>A is a canonical splice variant classified as pathogenic in the context of POMGNT-related disorders. c.1895+1G>A has been observed in cases with relevant disease (PMID: 15466003, 26908613). Functional assessments of this variant are not available in the literature. c.1895+1G>A has been observed in population frequency databases (gnomAD: SAS 0.003%). In summary, NM_017739.3(POMGNT1):c.1895+1G>A is a canonical splice variant that has been observed more frequently in cases with the relevant disease than in healthy populations. Please note: this variant was assessed in the context of healthy population screening. |
Broad Center for Mendelian Genomics, |
RCV002513697 | SCV003761148 | likely pathogenic | Muscular dystrophy-dystroglycanopathy | 2023-01-24 | criteria provided, single submitter | curation | The c.1895+1G>A variant in POMGNT1 has been previously reported in one individual, in the compound heterozygous state, with muscular dystrophy-dystroglycanopathy (PMID: 15466003), and has been identified in 0.003% (1/30416) of South Asian chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP ID: rs386834024). Although this variant has been seen in the general population in a heterozygous state, its frequency is low enough to be consistent with a recessive carrier frequency. This variant has also been reported in ClinVar (Variation ID#:56592) and has been interpreted as pathogenic by multiple labs. This variant is located in the 5’ splice region. Computational tools predict a splicing impact, though this information is not predictive enough to determine pathogenicity. Loss of function of the POMGNT1 gene is an established disease mechanism in autosomal recessive POMGNT1-associated muscular dystrophy-dystroglycanopathy. In summary, although although additional studies are required to fully establish its clinical significance, this variant is likely pathogenic for autosomal recessive POMGNT1-associated muscular dystrophy-dystroglycanopathy. ACMG/AMP Criteria applied: PVS1_moderate, PM2, PM3 (Richards 2015). |
Baylor Genetics | RCV001810415 | SCV004206004 | pathogenic | Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A3 | 2024-03-23 | criteria provided, single submitter | clinical testing | |
Gene |
RCV004700352 | SCV005201754 | pathogenic | not provided | 2023-06-01 | 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; Identified in a patient with a POMGNT1-related disorder who harbored an additional POMGNT1 variant (Diesen et al., 2004); This variant is associated with the following publications: (PMID: 25525159, 22323514, 15466003, 22554691, 26908613) |
Juha Muilu Group; Institute for Molecular Medicine Finland |
RCV000050005 | SCV000082414 | probable-pathogenic | Muscle eye brain disease | no assertion criteria provided | not provided | Converted during submission to Likely pathogenic. | |
OMIM | RCV000240866 | SCV000299363 | pathogenic | Retinitis pigmentosa 76 | 2012-07-15 | no assertion criteria provided | literature only | |
Natera, |
RCV000050005 | SCV002089576 | pathogenic | Muscle eye brain disease | 2020-10-21 | no assertion criteria provided | clinical testing |