Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Victorian Clinical Genetics Services, |
RCV000578154 | SCV000680005 | likely pathogenic | Autosomal recessive osteopetrosis 4 | 2017-01-17 | criteria provided, single submitter | clinical testing | A homozygous missense variant was identified, NM_001114331.2(CLCN7):c.1610G>A in exon 18 of the CLCN7 gene (chr16:1499082). This substitution is predicted to create a change of an arginine to a glutamine at amino acid position 537, NP_001107803.1(CLCN7):p.(Arg537Gln). The arginine at this position has low conservation and is not situated in a known functional domain. Grantham assessment is likely benign for this variant due to both conservation and amino acid properties. In silico software predicts this variant to be disease causing. This variant has not been previously observed in our patient cohort but is present in a population database at a very low frequency of 0.002% (ExAC). It has been previously reported in a child with osteopetrosis, neurodegeneration, retinal atrophy and tubulopathy, and was found to segregate with disease in the family (Besbas et al 2009 Eur J Pediatrics). Based on current information, this variant has been classified as LIKELY PATHOGENIC. |