Table 2. Classification of 12 mutations in crystallin genes in this study according to ACMG guideline.
| Family ID | Inheritance | Gene | cDNA change | p.change | Status | Type | PVS1 | PM1 | PM2 | PM4 | PP1 | PP2 | PP3 | PP5 | Classification | Reference |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| CAT-27 |
AD |
CRYAA |
c.35G>T |
p.R12L |
Hetero |
missense |
|
Y |
Y |
|
Y |
Y |
Y |
|
Likely pathogenic |
Novel |
| CAT-40 |
AD |
CRYAA |
c.346C>T |
p.R116C |
Hetero |
missense |
|
Y |
Y |
|
Y |
Y |
Y |
Y |
Likely pathogenic |
[17-20] |
| CAT-42 |
AD |
CRYAA |
c.61C>T |
p.R21W |
Hetero |
missense |
|
Y |
Y |
|
Y |
Y |
Y |
Y |
Likely pathogenic |
[12,21-24] |
| CAT-14 |
AD |
CRYBA1 |
IVS3 c.215+1G>A |
/ |
Hetero |
canonical splice site |
Y |
|
Y |
|
Y |
Y |
Y |
|
Pathogenic |
[25-28] |
| CAT-21 |
Sporadiccase |
CRYBA1 |
c.272-274GAG del |
p.G91del |
Hetero |
frameshift |
Y |
Y |
Y |
|
|
|
Y |
Likely pathogenic |
[29,30] |
|
| CAT-32 |
AD |
CRYBA1 |
IVS3 c.215+1G>A |
/ |
Hetero |
canonical splice site |
Y |
|
Y |
|
Y |
|
Y |
|
Pathogenic |
[25-28] |
| CAT-11 |
AD |
CRYBB2 |
c.463C>A |
p.Q155K |
Hetero |
missense |
|
Y |
Y |
|
Y |
Y |
Y |
|
Likely pathogenic |
Novel |
| CAT-44 |
AD |
CRYBB2 |
c.355G>A |
p.G119R |
Hetero |
missense |
|
Y |
Y |
|
Y |
Y |
Y |
Y |
Likely pathogenic |
[24] |
| CAT-24 |
AD |
CRYBB2 |
c.(433C>T; 440A>G; 449C>T) |
p.(R145W; Q147R; T150M) |
Hetero |
Complex missense |
Y |
|
|
|
Y |
Y |
Y |
Likely pathogenic |
[12,31] |
|
| CAT-53 |
Sporadiccase |
CRYBB2 |
c.(433C>T; 440A>G; 449C>T) |
p.(R145W; Q147R; T150M) |
Hetero |
Complex missense |
Y |
|
|
|
Y |
Y |
Y |
Likely pathogenic |
[12,31] |
|
| CAT-54 |
AD |
CRYBB2 |
c.(433C>T; 440A>G; 449C>T) |
p.(R145W; Q147R; T150M) |
Hetero |
Complex missense |
Y |
|
|
|
Y |
Y |
Y |
Likely pathogenic |
[12,31] |
|
| CAT-33 |
AD |
CRYGC |
IVS1 c.10-1G>A |
/ |
Hetero |
canonical splice site |
Y |
|
Y |
|
Y |
Y |
Y |
|
Pathogenic |
Novel |
| CAT-41 |
AD |
CRYGD |
c.346delT |
p.F116Sfsx29 |
Hetero |
frameshift |
Y |
Y |
Y |
Y |
|
|
|
Likely pathogenic |
Novel |
|
| CAT-46 | AD | CRYGD | c.70C>A | p.P24T | Hetero | missense | Y | Y | Y | Y | Y | Likely pathogenic | [24,31,31] | |||
Note: AD=autosomal dominant; Hetero=heterozygosity; PVS1=null variant (nonsense, frameshift, canonical +- 2 splice sites, initiation codon, single or multiexon deletion) in a gene where LOF is a known mechanism of disease PM1=Located in a mutational hot spot and/or critical and well established functional domain (e.g., active site of an enzyme) without benign variation; PM2=Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium; PM4=Protein length changes as a result of in-frame deletions/insertions in a nonrepeat region or stop-loss variants; PP1=Cosegregation with disease in multiple affected family members in a gene definitively known to cause the disease; PP2=Missense variant in a gene that has a low rate of benign missense variation and in which missense variants are a common mechanism of disease; PP3=Multiple lines of computational evidence support a deleterious effect on the gene or gene product (conservation, evolutionary, splicing impact, etc.) PP5=Reputable source recently reports variant as pathogenic, but the evidence is not available to the laboratory to perform an independent evaluation; PP6=The user has additional 2 supporting pathogenic evidences.