Table 1.
PKHD1 variants details
| Variant | Molecular consequence | db SNP ID | Accession number (ClinVar or HGMD) | Clinical significance on ClinVar/HGMD | Allele frequency (GnomADe) | SIFT [28] |
PolyPhen [29] |
CADD [30] |
REVEL [31] |
References |
|---|---|---|---|---|---|---|---|---|---|---|
| c.6900C > T; (p.Asn2300=) | synonymous | rs776060304 | VCV000558073 | Uncertain significance | T = 0.000016 (4/251312) | N/A | N/A | 9 (likely benign) | N/A | [32–34] |
| c.7964A > C; p.(His2655Pro) | missense | rs748196998 | CM163038 | Likely disease-causing | C = 0.000004 (1/251258) |
0 (deleterious) |
0.994 (probably damaging) | 24 (likely benign) | 0.819 (likely disease causing) | [35] |
| c.6900C > G; (p.Asn2300Lys) | missense | rs776060304 | VCV000552623 | Uncertain significance | N/A |
0 (deleterious) |
0.999 (probably damaging) | 22 (likely benign) | 0.489 (likely benign) | [36] |
| c.7964A > G; p.(His2655Arg) | missense | N/A | CM1612097 | Pathogenic | N/A |
0 (deleterious) |
0.990 (probably damaging) | 24 (likely benign) | 0.786 (likely disease causing) | [36] |
Molecular consequence, db SNP ID, variant accession number, clinical significance, allele frequency and pathogenicity prediction values according to a range of different algorithms for the two variants identified in the proband (c.6900C > T (p.Asn2300=); 7964A > C; p.(His2655Pro), in bold) and two different variants described in the literature that change the same nucleotides (c.6900C > G (p.Asn2300Lys); c.7964A > G; p.(His2655Arg))