Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000169064 | SCV000220228 | likely pathogenic | Infantile hypophosphatasia | 2014-04-09 | criteria provided, single submitter | literature only | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001264499 | SCV001442681 | likely pathogenic | Hypophosphatasia | 2020-10-03 | criteria provided, single submitter | clinical testing | Variant summary: ALPL c.791A>G (p.Lys264Arg) located in the exonic-splice region of exon 7 results in a conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. Several computational tools predict a significant impact on normal splicing: Four predict the variant abolishes a 5' splicing donor site. At least one publication reports experimental evidence that this variant affects mRNA splicing leading to a complete skipping of exon 7 (Brun-Heath_2007). The variant was absent in 251140 control chromosomes. c.791A>G has been reported in the literature in at-least one case of a baby girl affected with perinatal Hypophosphatasia (Brun-Heath_2007) as well as adults with this condition and subsequently cited by others (example, Taillandier_2018, Mornet_2008, Silvent_2014). These data indicate that the variant may be associated with disease. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Invitae | RCV001378582 | SCV001576184 | pathogenic | not provided | 2023-05-13 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Studies have shown that this missense change results in skipping of exon 7, but is expected to preserve the integrity of the reading-frame (PMID: 17922851). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 188750). This missense change has been observed in individual(s) with autosomal recessive hypophosphatasia (PMID: 17922851). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is present in population databases (rs786204442, gnomAD 0.3%). This sequence change replaces lysine, which is basic and polar, with arginine, which is basic and polar, at codon 264 of the ALPL protein (p.Lys264Arg). RNA analysis indicates that this missense change induces altered splicing and likely results in a shortened protein product. |
| Fulgent Genetics, |
RCV002498840 | SCV002775195 | likely pathogenic | Adult hypophosphatasia; Childhood hypophosphatasia; Infantile hypophosphatasia | 2022-01-14 | criteria provided, single submitter | clinical testing | |
| Baylor Genetics | RCV003462263 | SCV004195052 | likely pathogenic | Adult hypophosphatasia | 2023-06-20 | criteria provided, single submitter | clinical testing |