Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000169514 | SCV000220984 | likely pathogenic | Infantile hypophosphatasia | 2014-12-23 | criteria provided, single submitter | literature only | |
| Invitae | RCV001850403 | SCV002130241 | pathogenic | not provided | 2023-09-05 | 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: 189102). This premature translational stop signal has been observed in individual(s) with a child with hypophosphatasia (PMID: 20049532). This variant is present in population databases (rs755529290, gnomAD 0.003%). This sequence change creates a premature translational stop signal (p.Tyr297*) 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 | RCV003468845 | SCV004191870 | pathogenic | Adult hypophosphatasia | 2024-03-05 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004586588 | SCV005076076 | pathogenic | Hypophosphatasia | 2024-04-30 | criteria provided, single submitter | clinical testing | Variant summary: ALPL c.891C>A (p.Tyr297X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant allele was found at a frequency of 1.2e-05 in 251060 control chromosomes. c.891C>A has been reported as homozygous or compound heterozygous in the literature in individuals affected with early onset autosomal recessive Hypophosphatasia (e.g. Drury_2015, del Angel_2020). These data indicate that the variant is likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function (del Angel_2020). The most pronounced variant effect results in <10% of normal activity. The following publications have been ascertained in the context of this evaluation (PMID: 32160374, 26275891). ClinVar contains an entry for this variant (Variation ID: 189102). Based on the evidence outlined above, the variant was classified as pathogenic. |