Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Institute of Human Genetics, |
RCV001254174 | SCV001440335 | likely pathogenic | 8q24.3 microdeletion syndrome | 2020-09-07 | criteria provided, single submitter | clinical testing | |
| 3billion | RCV001254174 | SCV002012275 | pathogenic | 8q24.3 microdeletion syndrome | 2021-10-02 | criteria provided, single submitter | clinical testing | Frameshift: predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant (PVS1_VS). It is not observed in the gnomAD v2.1.1 dataset (PM2). The variant has been reported as pathogenic (ClinVar ID: VCV000976784.3). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline. |
| Centre de Biologie Pathologie Génétique, |
RCV001254174 | SCV002559173 | pathogenic | 8q24.3 microdeletion syndrome | criteria provided, single submitter | clinical testing | ||
| Clinical Genomics Program, |
RCV001254174 | SCV001427214 | pathogenic | 8q24.3 microdeletion syndrome | 2019-12-19 | no assertion criteria provided | clinical testing | The p.Asn207Profs*3 variant in the PUF60 gene was identified de novo in this individual, but has not been previously reported in association with disease. This variant was absent from large population databases, including the Genome Aggregation Database (http://gnomad.broadinstitute.org/). However, the ability to detect this type of variation is limited. This variant results in a 19 bp deletion, which causes a shift in the protein reading frame, leading to a premature termination codon 3 amino acids downstream. Heterozygous loss of function is an established mechanism of disease for the PUF60 gene. Additionally, a different nucleotide change (c.619_637del) resulting in an identical amino change (p.Asn207Profs*3) has been previously reported de novo in an individual with features consistent with Verheij syndrome and is expected to result in a similar disruption to protein function as c.612_630del (Low et al., 2017). These data were assessed using the ACMG/AMP variant interpretation guidelines. In summary, there is sufficient evidence to classify the p.Asn207Profs*3 variant as pathogenic for autosomal dominant Verheij syndrome based on the information above. [ACMG evidence codes used: PVS1, PS1, PS2_moderate, PM2_supporting] |