Submissions for variant NM_207122.2(EXT2):c.785dup (p.His262fs)

dbSNP: rs1555005328

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000599420	SCV000710358	pathogenic	not provided	2018-01-03	criteria provided, single submitter	clinical testing	The c.785dupA variant in the EXT2 gene has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. This duplication causes a frameshift starting with codon Histidine 262, changes this amino acid to a Glutamine residue and creates a premature Stop codon at position 3 of the new reading frame, denoted p.His262GlnfsX3. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.785dupA variant is not observed in large population cohorts (Lek et al., 2016). Based on currently available evidence, we consider c.785dupA to be pathogenic.
Invitae	RCV003497859	SCV004316741	pathogenic	Exostoses, multiple, type 2	2023-08-16	criteria provided, single submitter	clinical testing	This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.His262Glnfs*3) in the EXT2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in EXT2 are known to be pathogenic (PMID: 10679937, 19810120). This variant has not been reported in the literature in individuals affected with EXT2-related conditions. ClinVar contains an entry for this variant (Variation ID: 504053). For these reasons, this variant has been classified as Pathogenic.