TABLE 2.
Detailed characteristics of identified KAT6B variants.
| Patient | Molecular variant on cDNA (NM_012330.4) | Genomic coordinates (GRCh38) | Protein prediction (NP_036462.2) | Variant effect | KAT6B exon | Known/new variant | Genetic databases | Variant frequency in gnomAD v3.1.2 | Patient's phenotype | Inheritance | Variant evaluation according to ACMG/AMP criteria |
|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 | c.3852_3864del | chr10:g.75028676_75028688del | p.(Asp1284Glufs*46) | Frameshift | 18 | New | None | 0 | SBBYSS | de novo | Pathogenic (13 points): PVS1_very strong (8), PM2_moderate (2), PM6_moderate (2), PP4_supporting (1) |
| 2 | c.4026dup | chr10:g.75028850dup | p.(Pro1343Thrfs*4) | Frameshift | 18 | New | None | 0 | SBBYSS | de novo | Pathogenic (13 points): PVS1_very strong (8), PM2_moderate (2), PM6_moderate (2), PP4_supporting (1) |
| 3 | c.5819del | chr10:g.75030643del | p.(Gln1940Argfs*11) | Frameshift | 18 | New | None | 0 | SBBYSS | de novo | Pathogenic (13 points): PVS1_very strong (8), PM2_moderate (2), PM6_moderate (2), PP4_supporting (1) |
| 4 | c.3147G > A | chr10:g.75022006G > A | p.(Pro1049=) p.Ala1008Argfs*621 | Synonymous/splicing/frameshift | 16 | Known (6 unrelated patients)1,2 | HGMD (CM158570), Clinvar (ID 279815), dbSNP (rs886041207), ClinGen (CA10603048) | 0 | SBBYSS | de novo | Pathogenic (13 points): PS3_strong (4), PS4_strong (4), PM2_moderate (2), PM6_moderate (2), PP4_supporting (1) |
| 5 | c.4455dup | chr10:g.75029279dup | p.(Asn1486*) | Nonsense | 18 | New | None | 0 | SBBYSS | de novo | Pathogenic (13 points): PVS1_very strong (8), PM2_moderate (2), PM6_moderate (2), PP4_supporting (1) |
| 6 | c.5012del | chr10:g.75029836del | p.(Gly1671Alafs*44) | Frameshift | 18 | New | None | 0 | SBBYSS | de novo | Pathogenic (13 points): PVS1_very strong (8), PM2_moderate (2), PM6_moderate (2), PP4_supporting (1) |