Table 2:
Molecular characteristics of novel GCK variants
| Nucleotide | Amino Acida | Exon | GnomAD MAFb |
Polyphen Scorec |
SIFT Scored |
Human splice Finder |
Variant Classificatione |
Number of Families (Number of members) |
|---|---|---|---|---|---|---|---|---|
| c.37A>T | Lys13* | 1 | 0 | - | - | P | 1 (4) | |
| c.98T>A | Val33Glu | 2 | 0 | 0.99 | 0 | LP | 1 (1) | |
| c.215G>A | Gly72Glu | 3 | 0 | 1 | 0 | LP | 1 (3) | |
| c.295del | Trp99Glyfs*3 | 3 | 0 | - | - | P | 1 (1) | |
| c.317_333del | Gln106Argfs*9 | 3 | 0 | - | - | P | 1 (1) | |
| c.344dup | Met115Ilefs*6 | 3 | 0 | - | - | P | 1 (2) | |
| c.364C>A | Leu122Ile | 4 | 0 | 0.985 | 0 | LP | 1 (3) | |
| c.379T>C | Ser127Pro | 4 | 0 | 0.832 | 0 | VUS | 1 (1) | |
| c.422A>C | His141Pro | 4 | 0 | 0.99 | 0 | VUS | 1 (1)† | |
| c.503C>A | Thr168Asn | 5 | 0 | 1 | 0 | LP | 1 (7) | |
| c.511T>G | Phe171val | 5 | 0 | 1 | 0 | LP | 1 (1) | |
| c.540T>A | Asn180Lys | 5 | 0 | 1 | 0 | LP | 1 (1) | |
| c.554T>C | Leu185Pro | 5 | 0 | 1 | 0 | LP | 1 (3) | |
| c.554T>G | Leu185Arg | 5 | 0 | 1 | 0 | LP | 1 (1) | |
| c.579+4delA | Intron 5 | - | - | Alteration of the WT donor site | VUS | 1 (1) | ||
| c.619G>T | Val207leu | 6 | 0 | 0.998 | 0 | LP | 1 (3) | |
| c.630_632dup | Met210dup | 6 | 0 | LP | 2 (2,3) | |||
| c.632T>A | Ile211Asn | 6 | 0 | 1 | 0 | LP | 1 (1) | |
| c.678_679+2del | Gly227Hisfs*47 | 6 | 0 | - | - | P | 2 (3,1) | |
| c.680-2A>C | Intron 6 | - | - | Alteration of the WT acceptor site | P | 1 (2) | ||
| c.680G>A | Gly227Asp | 7 | 0 | 1 | 0 | LP | 1 (2) | |
| c.756C>G | Cys252Trp | 7 | 0 | 1 | 0 | LP | 1 (2) | |
| c.824G>T | Arg275Leu | 7 | 0 | 0.616 | 0 | LP | 1 (1) | |
| c.841T>C | Ser281Pro | 7 | 0 | 1 | 0 | LP | 1(1) | |
| c.848del | Asn283Thrfs*11 | 7 | 0 | - | - | P | 1 (1) | |
| c.908G>A | Arg303Gln | 8 | 0.0004081% | 1 | 0 | LP | 1 (1) | |
| c.919C>T | Leu307Phe | 8 | 0 | 0.718 | 0 | VUS | 1 (1)* | |
| c.951 C>G | His317Gln | 8 | 0 | 0.013 | 0.17 | VUS | 1 (2) | |
| c.1082dupC | T362Hisfs*97 | 9 | 0 | - | - | P | 1 (1) | |
| c.1113C>A | Cys371* | 9 | 0 | - | - | P | 1 (1) | |
| c.1130_1138del | Arg377_Ala379del | 9 | 0 | - | - | LP | 1 (3) | |
| c.1173C>A | Asn391Lys | 9 | 0 | 1 | 0 | LP | 1 (1) | |
| c.1181G>C | Arg394Pro | 9 | 0 | 0.99 | 0 | LP | 1 (1) | |
| c.1229G>A | Gly410Asp | 9 | 0 | 1 | 0 | LP | 1 (1) |
Abbreviations: gnomAD, Genome Aggregation Database; WT, Wild Type; MAF, Minor Allele Frequency; N/A, not available
a
RefSeq reference transcript: NM_000162.3 (GCK)
b
MAF from gnomAD was calculated using allele count / allele number.
c
Polyphen-2 scores range from 0.0 to 1.0 and can be interpreted as follows: 0.0 to 0.15 –benign, 0.15 to 0.85 --possibly damaging, 0.85 to 1.0 -- probably damaging.
d
SIFT scores range from 0.0 to 1.0 and can be interpreted as follows: 0.0 to 0.05 -deleterious, 0.05 to 1.0 - tolerated (benign)
e
Variants were classified according to the ACMG 5-tier system: P, pathogenic; LP, likely pathogenic; VUS, variant of uncertain significance.
†
Gestational diabetes
*
Presumed to be de novo