Submissions for variant NM_006031.6(PCNT):c.9535dup (p.Val3179fs)

dbSNP: rs747058622

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000319424	SCV000329667	pathogenic	not provided	2017-05-18	criteria provided, single submitter	clinical testing	The c.9535dupG pathogenic variant in the PCNT gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The c.9535dupG variant causes a frameshift starting with codon Valine 3179, changes this amino acid to a Glycine residue, and creates a premature Stop codon at position 36 of the new reading frame, denoted p.Val3179GlyfsX36. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.9535dupG variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Therefore, we interpret c.9535dupG as a pathogenic variant.
Revvity Omics, Revvity	RCV001782766	SCV002016555	pathogenic	Microcephalic osteodysplastic primordial dwarfism type II	2020-02-28	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000319424	SCV004616663	pathogenic	not provided	2024-01-05	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Val3179Glyfs*36) in the PCNT gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PCNT are known to be pathogenic (PMID: 18174396, 22821869). This variant is present in population databases (rs747058622, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with PCNT-related conditions. ClinVar contains an entry for this variant (Variation ID: 279984). For these reasons, this variant has been classified as Pathogenic.