Table 2 Analysis of likely pathogenic variants in familial and sporadic cataracts
From: Identification of mutations associated with congenital cataracts in nineteen Chinese families
Family | Gene | Transcript/ position | DNA Change | Predicted amino acid change | Mutation Type | Inheritance | ACMG Classification | SIFT/MutTaster/PolyPhen | CADD_Phred | REVEL | SpliceAI | AlphaMissence | GnomAD4_exome | ChinaMAP/WBBC | HGMD | Novel |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
1 | GJA3 | NM_021954.4 (chr13:20143113)) | c.176 C > T | p.P59L | nonsynonymous SNV | AD | LP ( PS4 + PM1 + PM2 + PP1 + PP3) | D/D/D | 29.4 | 0.97 | 0.0 | 0.86 | 0 | 0/0 | DM | Bennett, et al. 2004 |
2 | CRYGD | NM_006891.4 (chr2208121780) | c.418 C > T | p.R140* | stopgain | AD | P (PVS1 + PS3 + PS4 + PM2 + PM6 + PP1 + PP4) | - | 36 | - | 0.0 | - | 0 | 0/0 | DM | Jackson, et al. 2020 |
3 | CRYBA4 | NM_001886.3 (chr22:26630360) | c.464 C > T | p.P155L | nonsynonymous SNV | N/K | VUS (PM1 + PM2 + PP3) | D/D/D | 26.5 | 0.79 | 0.0 | 0.68 | 5.5e-6 | 0/0 | - | Yes |
4 | BFSP2 | NM_003571.4 (chr3:13348608–13348610) | c.697_699del | p.E233del | nonframeshift deletion | AD | LP ( PS4 + PM2 + PM4 + PP1) | - | - | - | 0.0 | - | 6.8e-7 | 0/0 | DM | Zhang, et al. 2004 |
5 | IARS2 | NM_018060.4 (chr1:220142958) | c.1067G > T | p.G356V | nonsynonymous SNV | AR | P (PM1 + PM2 + PM3) | - /D/D | 33 | 0.69 | 0.13 | 0.75 | 0 | 0/0 | - | Yes |
IARS2 | NM_018060.4 (chr1:220105891) | c.2575T > C | p.F859L | nonsynonymous SNV | VUS (PM1 + PM2 + PP3) | - /D/D | 31 | 0.38 | 0.0 | 0.97 | 1.9e-5 | 7.8e-4/7.8e-4 | DM | Li, et al. 2018 | ||
6 | CRYAA | NM_000394.4 (chr21:44589270) | c.61 C > T | p.R21W | nonsynonymous SNV | AD | P (PS3 + PS4 + PM2 + PM5 + PP1 + PP3) | D/D/D | 29.6 | 0.89 | 0.0 | 0.86 | 0 | 0/0 | DM | Hansen, et al.2007 |
7 | GJA3 | NM_021954.4 (chr13:20142700) | c.589 C > T | p.P197S | nonsynonymous SNV | AD | LP (PM1 + PM2 + PP1 + PP3 + PP4) | D/D/D | 27.8 | 0.97 | 0.01 | 0.96 | 0 | 0/0 | DM | Ponnam et al. 2013 |
8 | CRYBA1 | NM_005208.5 (chr17:29242117–29242119) | c.272_274del | p.G91del | nonframeshift deletion | AD | P (PS2 + PS3 + PS4 + PM1 + PM2 + PM4 + PP1) | - | - | - | 0.0 | - | 1.4e-6 | 0/0 | DM | Lu, et al. 2007 |
9 | ARL2 | NM_001667.4 (chr11:65014251) | c.44G > T | p.R15L | nonsynonymous SNV | AD | LP (PS3 + PM2 + PM6 + PP1) | D/D/B | 27.3 | 0.99 | 0.0 | 0.68 | 3.05-5 | 1.7e-3/1.7e-3 | DM | Cai, et al. 2019 |
10 | CRYBB3 | NM_004076.5 (chr22:25201254) | c.-20-123G > C | - | splicing variant | N/K | VUS (PM2 + PM3) | - | 12 | - | 0.23 | - | 7.2e-6 | 1.5e-4/1.1e-4 | - | Yes |