TABLE 1.
Possibly causative variants detected in sequence analyses
| Patient | Gene | Nucleotide change | Amino acid change | Zygocity | RefSeq | Allele frequency (gnomAD total) | Allele frequency (gnomAD Finnish) | CADD Phred | Phenotype MIM number |
|---|---|---|---|---|---|---|---|---|---|
| 1000 a | COL4A1 | c.*36T>Ab | . | Het | NM_001845.6 | 0 | 0 | . | 618564 |
| 1001 | TUBB2A | c.1309G>A | p.(Glu437Lys) | Het | NM_001069.3 | 0 | 0 | 23.1 | 615763 |
| 1006 | COLGALT1 | c.1411C>T | p.(Arg471Trp) | Het | NM_024656.3 | 0.00001315 | 0 | 33 | 618360 |
| 1007 | UBQLN2 | c.304A>G | p.(Ile102Val) | Hem | NM_013444.4 | 0.000008916 | 0.0001623 | 25.6 | 300857 |
| 1015 | C1R | c.716G>A | p.(Arg239Gln) | Het | NM_001354346.2 | 0.000006572 | 0 | 26.5 | 130080 |
| 1016 | PRNP | c.713C>T | p.(Pro238Leu) | Het | NM_000311.5 | 0 | 0 | 23.9 | 137440, 123400, 603218, 600072, 606688 |
| 1017 | PCNT | c.2179C>G | p.(His727Asp) | Het | NM_006031.6 | 0 | 0 | 23.0 | 210720 |
| 1017 | VPS13A | c.9257T>C | p.(Met3086Thr) | Het | NM_033305.3 | 0 | 0 | 21.8 | 200150 |
| 1017 | SMAD4 | c.1060G>A | p.(Val354Met) | Het | NM_005359.5 | 0 | 0 | 26.1 | 175050 |
| 1019 | CHMP2B | c.157G>C | p.(Gly53Arg) | Het | NM_014043.4 | 0.000006578 | 0.00009448 | 28.3 | 600795 |
| 1020 | GRIN2A | c.937A>G | p.(Ile313Val) | Het | NM_000833.5 | 0.000006573 | 0.00009418 | 22.4 | 245570 |
| 1025 | DIAPH1 | c.1093T>C | p.(Phe365Leu) | Het | NM_005219.5 | 0.00007229 | 0.0007529 | 25.7 | |
| 1027 | TSC2 | c.4432G>A | p.(Asp1478Asn) | Het | NM_000548.5 | 0 | 0 | 29.0 | 613254 |
| 1029 | MTHFR | c.1061G>C | p.(Gly354Ala) | Hom | NM_001330358.2 | 0.0001839 | 0.002541 | 25.5 | 236250 |
| 1030 | HTRA1 | c.847G>A | p.(Gly283Arg) | Het | NM_002775.5 | 0 | 0 | 33 | 600142, 616779 |
| 1033 | THSD1 | c.1619dupT | p.(Met540fs) | Het | NM_018676.4 | 0 | 0 | . | 618734 |
| 1033 | SNCA | c.370G>T | p.(Ala124Ser) | Het | NM_000345.4 | 0.00001315 | 0.0001886 | 19.55 | 127750, 168601, 605543 |
| 1036 | CCM2 | c.391G>A | p.(Asp131Asn) | Het | NM_001029835.2 | 0.0001840 | 0.0002825 | 28.2 | 603284 |
| 1038 | DNAJC13 | c.1036C>G | p.(Leu346Val) | Het | NM_015268.4 | 0.00001314 | 0.0001885 | 21.6 | 616361 |
| 1039 | SLC20A2 | c.1858C>T | p.(Arg620Trp) | Het | NM_006749.5 | 0.00002631 | 0 | 28.9 | 213600 |
| 1043 | NMNAT2 | c.427G>A | p.(Val143Met) | Het | NM_015039.4 | 0 | 0 | 21.3 | . |
| 1045 | POLG | c.2218A>G | p.(Asn740Asp) | Het | NM_002693.3 | 0.00005260 | 0 | 22.6 | 203700, 613662, 607459, 157640, 258450 |
| 1045 | TREX1 | c.1079A>G | p.(Tyr360Cys) | Het | NM_016381.5 | 0.0001314 | 0 | 24.9 | 192315 |
All variants were classified as being of unknown significance based on ACMG guidelines
Abbreviations: Hem, hemizygous; Het, heterozygous; Hom, homozygous; MIM, Mendelian Inheritance in Man.
CADD Combined Annotation Dependent Depletion, algorithm for scoring the deleteriousness of variants (≥10 = belongs to 10% of the most deleterious variants in the human genome, ≥20 = belongs to 1% of the most deleterious variants in the human genome).
a
Sample 1000 was not exome‐sequenced, COL4A1 variant c.*36T>A was detected by sanger sequencing.
b
Although the COL4A1 variant c.*36T>A is of interest, pending further evidence and information, we classify it as a variant of unknown significance.