Submissions for variant NM_007055.4(POLR3A):c.2005C>T (p.Arg669Ter)

gnomAD frequency: 0.00001  dbSNP: rs774007232

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Cole/Wambach Lab,Washington University in St. Louis	RCV000755668	SCV000886475	pathogenic	Neonatal pseudo-hydrocephalic progeroid syndrome	2018-10-01	criteria provided, single submitter	research
GeneDx	RCV000760689	SCV000890581	pathogenic	not provided	2018-08-20	criteria provided, single submitter	clinical testing	The R669X nonsense variant in the POLR3A gene has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. Furthermore, the R669X variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). We interpret R669X as a pathogenic variant.
Invitae	RCV000760689	SCV001397179	pathogenic	not provided	2021-09-15	criteria provided, single submitter	clinical testing
Kasturba Medical College, Manipal, Manipal Academy of Higher Education	RCV000755668	SCV001478355	pathogenic	Neonatal pseudo-hydrocephalic progeroid syndrome	2019-05-12	criteria provided, single submitter	clinical testing
OMIM	RCV000755668	SCV000883070	pathogenic	Neonatal pseudo-hydrocephalic progeroid syndrome	2022-05-24	no assertion criteria provided	literature only
University of Washington Center for Mendelian Genomics, University of Washington	RCV000755668	SCV001479498	likely pathogenic	Neonatal pseudo-hydrocephalic progeroid syndrome		no assertion criteria provided	research
Genomics England Pilot Project,Genomics England	RCV001542770	SCV001760258	likely pathogenic	Leukoencephalopathy-ataxia-hypodontia-hypomyelination syndrome		no assertion criteria provided	clinical testing