Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Embryology Laboratory, |
RCV000496104 | SCV000540920 | pathogenic | Congenital NAD deficiency disorder | 2016-12-23 | criteria provided, single submitter | research | This variant was discovered in a consanguineous family of Middle East origin. The patient presented multiple congenital malformations affecting vertebrae, heart and kidney among others. This variant is a protein truncating variant and novel (ExAC MAF 0). The patient is homozygous, while her unaffected parents and three unaffected siblings are heterozygous for this variant. The patient showed increased plasma concentration of 3HAA and reduced plasma concentration of NAD, consistent with loss of function of the HAAO enzyme activity. Enzyme assay confirmed that the protein product of this gene variant has lost enzyme activity. Mouse embryos homozygous null for Haao presented similar phenotype as observed in the patient, and also showed reduced concentration of NAD in the embryonic tissue. |
| SIB Swiss Institute of Bioinformatics | RCV000505813 | SCV000787463 | pathogenic | Vertebral, cardiac, renal, and limb defects syndrome 1 | 2018-04-16 | criteria provided, single submitter | curation | This variant is interpreted as a Pathogenic, for Vertebral, cardiac, renal, and limb defects syndrome 1, Autosomal Recessive inheritance. The following ACMG Tag(s) were applied: PM2 => Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium. PVS1-Strong => PVS1 downgraded in strength to Strong. PS3 => Well-established functional studies show a deleterious effect (PMID:28792876). |
| OMIM | RCV000505813 | SCV000599999 | pathogenic | Vertebral, cardiac, renal, and limb defects syndrome 1 | 2017-09-21 | no assertion criteria provided | literature only |