Table 1.
Congenital erythrocytosis on NGS panel (N = 6).
| Patient | Age at Diagnosis | Sex | Hb (g/L), Hct (%), RBC (T/L) | EV/PV Test | EPO (mU/mL) | Gene | Accession-Nr. | Variant | dbSNP ID | Zygosity | Inheritance | ACMG Classification |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 | 32 | M | 181, 54, 5.88 | Absolute erythrocytosis | 16.4 (normal) | EPO | NM_000799.4 | c.*656G>A | rs1186897562 | het | AD | VUS (PM2, BP7) |
| 2 | 34 | M | 195, 57, 5.89 | Absolute erythrocytosis | 8.45 (normal) | EGLN1 | NM_022051.2 | c.1088T>G p.(Leu363Arg) | N/A | het | AD | Likely pathogenic (PM1, PM2, PP2, PP3) |
| 3 | 80 | M | 207, 60, NA | NA | 7.6 (normal) | EGLN1 | NM_022051.3 | c.122_124delACT, p.(Tyr41del) | rs1182227189 | het | AD | Likely pathogenic (PM1, PM2, PM4) |
| 4 | 20 | M | 192, 56, 6.48 | Absolute erythrocytosis | 6.6 (normal) | VHL | NM_000551.4 | c.340+648T>C | rs73024533 | het | AR/AD | VUS (PM2) |
| 5 | 22 | M | 170, 48, 5.48 | NA | 11.09 (normal) | EPAS1 | NM_001430.5 | c.466G>T, p.(Gly156Trp) | rs377257704 | het | AD | VUS (PM2, PP3) |
| JAK2 | NM_004972.4 | c.1711G>A, p.(Gly571Ser) | rs139504737 | het | AD/somatic | VUS (PM2, PP3, BS3) | ||||||
| 6 | 27 | M | 174, 47, 5.54 | Absolute erythrocytosis | 6.06 (normal) | JAK2 | NM_004972.4 | c.1169C>T, p.(Pro390Leu) | rs768074072 | het | AD/somatic | VUS (PM2, PP3) |
| SH2B3 | NM_005475.3 | c.107C>A, p.(Ala36Glu) | rs574829930 | het | AD/somatic | VUS (PM2) |
Genes tested (N = 13): EPOR (exons 7, 8), VHL (orf including exon 1′), EGLN1, EPAS1, EPO (including several regulatory regions), JAK2 (exons 12–16), BPGM, HBB, HBA1, HBA2, HIF3A, OS9, SH2B3 somatic. Method: Ion AmpliSeq custom gene panel, sequencing on Thermo Fisher Ion Torrent S5. Interpretation: Only gene variants of the categories pathogenic, likely pathogenic and variant of unknown significance (VUS) according to ACMG guidelines 2015 are mentioned. Abbreviations: AR: autosomal recessive, AD: autosomal dominant; EPO: erythropoietin. EV/PV: erythrocyte volume to plasma volume, F: female, het: heterozygous, M: male, VUS: variant of unknown significance.