Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000754488 | SCV000804206 | uncertain significance | not provided | 2018-08-01 | criteria provided, single submitter | clinical testing | The c.912_917delTTACAT variant in the DHPS gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The c.912_917delTTACAT variant causes an in-frame deletion of two amino acids, Tyrosine 305 and Isoleucine 306, denoted p.Tyr305_Ile306del. The Y305 residue is not conserved, and for the I306 residue, amino acids with similar properties to Isoleucine are tolerated across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. The c.912_917delTTACAT variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). We interpret c.912_917delTTACAT as a variant of uncertain significance. |
| SIB Swiss Institute of Bioinformatics | RCV000786002 | SCV001194271 | likely pathogenic | Neurodevelopmental disorder with seizures and speech and walking impairment | 2019-10-22 | criteria provided, single submitter | curation | This variant is interpreted as Likely pathogenic for Neurodevelopmental disorder with seizures and speech and walking impairment, autosomal recessive. The following ACMG Tag(s) were applied: PM2, PM3, PS3-Moderate. |
| Prevention |
RCV003420196 | SCV004117713 | likely pathogenic | DHPS-related disorder | 2023-09-07 | criteria provided, single submitter | clinical testing | The DHPS c.912_917del6 variant is predicted to result in an in-frame deletion (p.Tyr305_Ile306del). This variant has been reported in the compound heterozygous state with a second putative disease-allele in an individual with neurodevelopmental delay and seizures (Ganapathi et al. 2019. PubMed ID: 30661771). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare in the general population. Functional analysis indicated that this variant strongly reduces DHPS enzyme activity (Ganapathi et al. 2019. PubMed ID: 30661771; Padgett et al. 2023. PubMed ID: 37333770). Taken together, this variant is classified as likely pathogenic. |
| OMIM | RCV000786002 | SCV000924641 | pathogenic | Neurodevelopmental disorder with seizures and speech and walking impairment | 2019-06-24 | no assertion criteria provided | literature only |