Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001290555 | SCV001478627 | pathogenic | Hypophosphatasia | 2023-08-10 | criteria provided, single submitter | clinical testing | Variant summary: ALPL c.662delG (p.Gly221ValfsX56) results in a premature termination codon, predicted to cause absence of the protein due to nonsense mediated decay, a commonly known mechanism for disease. The variant allele was found at a frequency of 8e-06 in 251452 control chromosomes (gnomAD). c.662delG has been reported in the literature as a compound heterozygous genotype in at least three individuals affected with autosomal recessive Hypophosphatasia, including at least one case with perinatal onset (e.g. Spentchian_2003, Glotov_2022). These data indicate that the variant is likely associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 33191482, 12815606, 36361766). One submitter has cited a clinical-significance assessment for this variant to ClinVar after 2014 and has classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
| Invitae | RCV001863158 | SCV002238713 | pathogenic | not provided | 2022-09-22 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 996236). This premature translational stop signal has been observed in individual(s) with hypophosphatasia (PMID: 12815606). This variant is present in population databases (rs769948289, gnomAD 0.0009%). This sequence change creates a premature translational stop signal (p.Gly221Valfs*56) in the ALPL gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ALPL are known to be pathogenic (PMID: 3174660, 10679946, 32973344, 33814268). |
| Baylor Genetics | RCV003469505 | SCV004192539 | pathogenic | Adult hypophosphatasia | 2023-08-10 | criteria provided, single submitter | clinical testing |