Table 3 Variants with an increase in pathogenicity score due to reanalysis
From: Genomic diagnosis for children with intellectual disability and/or developmental delay
Gene | Affected individual ID(s) | Variant info | Original score | Updated score | Reason(s) for update | Evidence for upgrade |
|---|---|---|---|---|---|---|
DDX3X | 00075-C | NM_001356.4(DDX3X):c.745G > T (p.Glu249Ter) | VUS | Pathogenic | Publication | [38] |
EBF3 | 00006-C | NM_001005463.2(EBF3):c.1101 + 1G > T | VUS | Pathogenic | GeneMatcher | Collaboration with several other groups identified patients with comparable genotypes and phenotypes [37] |
EBF3 | 00032-C | NM_001005463.2(EBF3):c.530C > T (p.Pro177Leu) | VUS | Pathogenic | GeneMatcher | Collaboration with several other groups identified patients with comparable genotypes and phenotypes [37] |
KIAA2022 | 00082-C | NM_001008537.2(KIAA2022):c.2999_3000delCT (p.Ser1000Cysfs) | VUS | Pathogenic | Publication/Personal communication | [39] |
TCF20 | 00078-C | NM_005650.3(TCF20):c.5385_5386delTG (p.Cys1795Trpfs) | VUS | Pathogenic | Publication | [16] |
ARID2 | 00026-C | NM_152641.2(ARID2):c.1708delT (p.Cys570Valfs) | NR | Pathogenic | Publication | [40] |
CDK13 | 00253-C | NM_003718.4(CDK13):c.2525A > G (p.Asn842Ser) | NR | Pathogenic | Publication | [16] |
CLPB | 00127-C | NM_030813.5(CLPB):c.1222A > G (p.Arg408Gly) NM_030813.5(CLPB):c.1249C > T (p.Arg417Ter) | NR | Pathogenic | Publication | [41] |
FGF12 | 00074-C | NM_021032.4(FGF12):c.341G > A (p.R114H) | NR | Pathogenic | Publication | [42] |
MTOR | 00040-C | NM_004958.3(MTOR):c.4785G > A (p.Met1595Ile) | NR | Pathogenic | Publication | |
MTOR | 00028-C, 00028-C2 | NM_004958.3(MTOR):c.5663 T > G (p.Phe1888Cys) | NR | Pathogenic | Filter | In original filter, required allele count of one; this variant was present in identical twins |
HDAC8 | 00001-C | NM_018486.2(HDAC8):c.737 + 1G > A | NR | Likely pathogenic | Filter | In original filter, required depth for all members of trio was set to 10 reads; father had only 7 |
LAMA2 | 00055-C, 00055-S | NM_000426.3(LAMA2):c.715C > T (p.Arg239Cys) | NR | Likely pathogenic | Clarification of clinical phenotype | Discussion with clinicians was necessary to determine that patients’ phenotypes did match those observed for LAMA2 |
MAST1 | 00270-C | NM_014975.2:c.278C > T, p.Ser93Leu | NR | Likely pathogenic | GeneMatcher | Collaboration with several other groups identified patients with comparable genotypes and phenotypes |
SUV420H1 | 00056-C | NM_017635.3:c.2497G > T, p.Glu833X | NR | Likely pathogenic | Publication | [16] |