Submissions for variant NM_001351132.2(PEX5):c.449-2A>G

dbSNP: rs1555176945

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000598525	SCV000706508	pathogenic	not provided	2017-02-22	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV004689804	SCV005186037	likely pathogenic	PEX5-related disorder	2024-05-02	criteria provided, single submitter	clinical testing	Variant summary: PEX5 c.449-2A>G is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Several computational tools predict a significant impact on normal splicing: Four predict the variant abolishes a 3' acceptor site. However, these predictions have yet to be confirmed by functional studies. The frequency data for this variant in gnomAD is considered unreliable, as metrics indicate poor data quality at this position. To our knowledge, no occurrence of c.449-2A>G in individuals affected with PEX5-Related Disorders and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 500513). Based on the evidence outlined above, the variant was classified as likely pathogenic.