Submissions for variant NM_000098.3(CPT2):c.764A>G (p.Asp255Gly)

dbSNP: rs199673903

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Center for Molecular Medicine, Children’s Hospital of Fudan University	RCV001030039	SCV001190557	likely pathogenic	Carnitine palmitoyl transferase II deficiency, neonatal form	2019-05-10	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003396622	SCV004122510	uncertain significance	not specified	2023-10-02	criteria provided, single submitter	clinical testing	Variant summary: CPT2 c.764A>G (p.Asp255Gly) results in a non-conservative amino acid change located in the Choline/carnitine acyltransferase domain (IPR039551) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 251162 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.764A>G has been reported in the literature in at least one compound heterozygous individual affected with Carnitine Palmitoyltransferase II Deficiency (e.g., Yang_2020, Wang 2020). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 32411386, 31501239). One submitter has reported clinical-significance assessments for this variant to ClinVar after 2014 and has classified the variant as likely pathogenic without evidence for independent evaluation. Based on the evidence outlined above, the variant was classified as uncertain significance.