ClinVar Miner

Submissions for variant NM_012205.3(HAAO):c.483dup (p.Asp162Ter)

gnomAD frequency: 0.00001  dbSNP: rs527656756
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Embryology Laboratory, Victor Chang Cardiac Research Institute RCV000496188 SCV000540919 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 extremely rare (ExAC MAF 0.00003005). The patient is homozygous, while his unaffected parents and four 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 RCV000505810 SCV000787492 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 RCV000505810 SCV000599998 pathogenic Vertebral, cardiac, renal, and limb defects syndrome 1 2017-09-21 no assertion criteria provided literature only

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