| Family / reported phenotype | Human *RSPO2* variant (HGVS as reported) | Variant type | Functional / phenotype inference |
|---|---|---|---|
| F1 — HFH-RTRD; **4 affected fetuses** | c.205C>T; p.Arg69Cys | Homozygous missense | Hypomorphic allele: reduced receptor/ligase binding and reduced WNT potentiation; associated with the comparatively milder humerofemoral hypoplasia with radiotibial ray deficiency phenotype. (pqac-00000006, pqac-00000015) |
| F2 — TETAMS | c.208C>T; p.Gln70* | Homozygous nonsense | Functionally null-like in the reported assays; associated with severe tetra-amelia syndrome. F2–F5 together comprised **7 affected fetuses**; the publication does not support assigning that combined count to this family individually. (pqac-00000006, pqac-00000015, pqac-00000040) |
| F3 — TETAMS | ~154-kb homozygous deletion involving intron 5 and exon 6; reported coordinate chr8:108,809,266–108,963,256 (**genome build unspecified here**) | Structural deletion / predicted loss of function | Exon-disrupting biallelic deletion associated with severe tetra-amelia syndrome; identified by SNP array/array-CGH. F2–F5 collectively had 7 affected fetuses. (pqac-00000007, pqac-00000009, pqac-00000040) |
| F4 — TETAMS | c.409G>T; p.Glu137* | Homozygous nonsense | Predicted truncating loss-of-function allele associated with severe tetra-amelia syndrome; no independent family-specific affected count should be inferred from the combined F2–F5 total. (pqac-00000006, pqac-00000007, pqac-00000040) |
| F5 — TETAMS | c.123delG; p.Gly42Valfs*49 | Homozygous frameshift | Predicted early truncating loss of function associated with severe tetra-amelia syndrome; F2–F5 together comprised 7 affected fetuses. (pqac-00000006, pqac-00000007, pqac-00000040) |
| Evidence boundary | Primary report: Szenker-Ravi et al., *Nature* (May 2018), DOI [10.1038/s41586-018-0118-y](https://doi.org/10.1038/s41586-018-0118-y), PMID [29769720](https://pubmed.ncbi.nlm.nih.gov/29769720/) | Five-family allelic series | Case counts are **ascertained-cohort observations, not population frequencies**. Variant descriptions and functional interpretations are from the primary publication; this table does **not** assert independently verified ClinVar classifications or formal variant-by-variant ACMG/AMP classifications. (pqac-00000006, pqac-00000007, pqac-00000015) |


*Table: Evidence-checked summary of the five-family 2018 RSPO2 allelic series, separating the four milder F1 cases from the seven severe TETAMS fetuses distributed collectively across F2–F5. Counts are cohort observations, and no independent ClinVar or ACMG/AMP classifications are asserted.*