Table 2.
Identified biallelic variants of DNAH12 and ICSI outcomes in three infertile Chinese men
| Subject | AY0749 | NJ0278 | XM0178 | ||||
|---|---|---|---|---|---|---|---|
| cDNA Mutation | c.9004C>T | c.2448A>G | c.6229C>T | c.8293-1G>C | c.4476 + 5G>A | ||
| Protein Alteration | p.Arg3002Cys | p.Ile816Met | p.Gln2077X | – | – | ||
| Mutation Type | Missense | Missense | Stop-gain | Splicing | Splicing | ||
| Affected Allele | Het | Het | Hom | Het | Het | ||
| ACMG classification | VUS | VUS | VUS | VUS | VUS | ||
| Allele Frequency in Population | |||||||
| 1KGP | 0 | 2.20E-03 | 0 | 0 | 0 | ||
| gnomAD | 1.28E-05 | 5.00E-04 | 2.71E-05 | 0 | 0 | ||
| gnomAD-EAS | 9.18E-05 | 6.30E-03 | 4.00E-04 | 0 | 0 | ||
| Function prediction | |||||||
| SIFT | B | D | NA | NA | NA | ||
| PolyPhen-2 | D | D | NA | NA | NA | ||
| Mutation Taster | D | B | D | D | NA | ||
| CADD | 29.4 | 24.6 | 38 | 25 | 23.6 | ||
| Splicing prediction | Score (threshold) | ||||||
| spliceAI | – | – | – | 0.9579(>0.1) | 0.8813(>0.1) | ||
| dbscSNV ADA | – | – | – | 1.0(>0.6) | 0.9998(>0.6) | ||
| dbscSNV RF | – | – | – | 0.9440(>0.6) | 0.9260(>0.6) | ||
| SPiCE | – | – | – | 1.0(>0.115) | 0.9999(>0.115) | ||
| ICSI outcomes | |||||||
| Male age (years) | 31 | 41 | 33 | ||||
| Female age (years) | 28 | 37 | 31 | ||||
| No. of ICSI cycles | 1 | 1 | 1 | ||||
| No. of oocytes retrieved | 17 | 14 | 16 | ||||
| No. of oocytes injected | 11 | 14 | 16 | ||||
| Fertilization rate (%) | 100（11/11） | 100（14/14） | 93.8（15/16） | ||||
| Cleavage rate (%) | 90.9（10/11） | 100（14/14） | 93.3（14/15） | ||||
| 8-Cell formation rate (%) | 63.6（7/11） | 50.0（7/14） | 42.9（6/14） | ||||
| Blastocyst formation rate (%) | 54.5（6/11） | 21.4（3/14） | 58.3（7/12） | ||||
| High quality blastocyst rate (%) | 36.4（4/11） | 21.4（3/14） | 33.3（4/12） | ||||
| No. of transfer cycles | 1 | 1 | – | ||||
| Number of embryos transferred per cycle | 1 | 1 | – | ||||
| Implantation rate (%) | 100 | 100 | – | ||||
| Clinical pregnancy rate per transfer cycle (%) | 100 | 100 | – | ||||
| Miscarriage rate (%) | 0 | 100 | – | ||||
| Delivery | 1 | 0 | – | ||||
RefSeq accession number of DNAH12 is ENST00000351747; Variants with CADD values greater than 20 are considered to be deleterious; Abbreviations: 1KGP, 1000 Genomes Project; gnomAD, the Genome Aggregation Database; VUS: variant of uncertain significance; NA, not available; B, benign; D, damaging; ICSI: intracytoplasmic sperm injection.