Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
New York Genome Center | RCV003336032 | SCV004046541 | likely pathogenic | Mullegama-Klein-Martinez syndrome; Holoprosencephaly 13, X-linked | 2023-03-29 | criteria provided, single submitter | clinical testing | The c.3222dup variant identified in the STAG2 gene has not previously been reported in literature or public variant repositories (ClinVar and HGMD) and is absent from population databases (gnomAD v2.1.1 and v3.1.2, TOPMed Freeze 8), suggesting it is not a common benign variant in the populations represented in those databases. The c.3222dup variant in STAG2, located in exon 30 of this 35-exon gene, is predicted to incorporate a premature termination codon (p.(Ser1075IlefsTer12)) leading to loss-of-function via nonsense mediated decay; however, there are no functional studies to support or refute these predictions. Although the majority of reported loss-of-function variants in literature are upstream of c.3222dup, a downstream loss-of-function variant has been identified in an affected individual [PMID: 32058062]. Based on available evidence the c.3222dup p.(Ser1075IlefsTer12) variant identified in STAG2 is classified as Likely Pathogenic. |