Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
SIB Swiss Institute of Bioinformatics | RCV001030767 | SCV001432983 | likely pathogenic | Neurodevelopmental disorder with microcephaly and dysmorphic facies | 2020-09-10 | criteria provided, single submitter | curation | This variant is interpreted as likely pathogenic for Nabais Sa-de Vries syndrome 1, autosomal dominant. The following ACMG Tag(s) were applied: Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium (PM2); De novo (paternity and maternity confirmed) (PS2); Missense variant in a gene that has a low rate of benign missense variation and in which missense variants are a common mechanism of disease (PP2). Well-established functional studies show a deleterious effect (PS3 downgraded to supporting). |
Ambry Genetics | RCV001265939 | SCV001444111 | likely pathogenic | Inborn genetic diseases | 2020-11-02 | criteria provided, single submitter | clinical testing | The c.362G>A (p.R121Q) alteration is located in exon 7 (coding exon 4) of the SPOP gene. This alteration results from a G to A substitution at nucleotide position 362, causing the arginine (R) at amino acid position 121 to be replaced by a glutamine (Q). Based on data from the Genome Aggregation Database (gnomAD), the SPOP c.362G>A alteration was not observed, with coverage at this position. The SPOP c.362G>A (p.R121Q) alteration was observed de novo in a patient with congenital microcephaly, sensorineural hearing loss, mild intellectual disability, behavioral abnormalities, and craniofacial dysmorphisms including a small forehead, highly arched eyebrows, blepharophimosis, a full nasal tip, flat philtrum, micrognathia, and a pointed chin (Nabais Sá, 2020). The p.R121 amino acid is conserved in available vertebrate species. The in silico prediction for the p.R121Q alteration is inconclusive. Based on the available evidence, this alteration is classified as likely pathogenic. |
Gene |
RCV002272391 | SCV002558573 | pathogenic | not provided | 2022-01-13 | criteria provided, single submitter | clinical testing | Published functional studies indicate that the variant results in reduced BET expression through a gain-of-function mechanism (Nabais et al., 2020; Janouskova et al., 2017); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 31026449, 25766326, 28805821, 32109420) |
OMIM | RCV001030767 | SCV001194275 | pathogenic | Neurodevelopmental disorder with microcephaly and dysmorphic facies | 2020-05-01 | no assertion criteria provided | literature only |