Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Institute for Genomic Medicine, |
RCV004771379 | SCV005380244 | likely pathogenic | Pseudohypoparathyroidism type I A | 2024-10-23 | criteria provided, single submitter | research | The c.432+5G>A variant was identified in a patient with short stature and her affected mother, in whom it arose de novo. It is absent from gnomADv4.1, All Of Us, and RGC-ME databases, making it extremely rare. Although it does not affect the splice donor site, this variant alters the conserved +5 base after exon 5 and is predicted to disrupt splicing by SpliceAI and Pangolin. RNA-Seq of patient blood demonstrated multiple splicing abnormalities (exon 5 skipping, intron 5 retention, and activation of cryptic splice donor sites). We interpret this variant as Likely Pathogenic. |