Submissions for variant NM_207122.2(EXT2):c.626+3A>C

gnomAD frequency: 0.00003  dbSNP: rs200934340

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
St. Jude Molecular Pathology, St. Jude Children's Research Hospital	RCV001543120	SCV001761637	uncertain significance	Multiple congenital exostosis	2021-06-24	criteria provided, single submitter	clinical testing	The EXT2 c.725+3A>C intronic change results from a A to C substitution at the +3 position of intron 4 of the EXT2 gene. Splice predictors are not conclusive as to whether or not this variant affects splicing and loss of function of the resulting protein product. RNA data demonstrates aberrant splicing in ~6-7% of mutant reads (internal data). This variant has a maximum subpopulation frequency of 0.0023% in gnomAD v2.1.1 (PM2_Supporting; https://gnomad.broadinstitute.org/variant/11-44130836-A-C?dataset=gnomad_r2_1). In summary, this variant meets criteria to be classified as of uncertain significance based on the ACMG/AMP criteria: PM2_Supporting.
GeneDx	RCV001564582	SCV001787767	uncertain significance	not provided	2021-04-14	criteria provided, single submitter	clinical testing	Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports a deleterious effect on splicing; Has not been previously published as pathogenic or benign to our knowledge