Submissions for variant NM_003560.4(PLA2G6):c.1427+1G>C

dbSNP: rs750939090

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV001266198	SCV001444370	likely pathogenic	Inborn genetic diseases	2018-01-08	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV002469366	SCV002766230	likely pathogenic	Neurodegeneration with brain iron accumulation	2022-11-29	criteria provided, single submitter	clinical testing	Variant summary: PLA2G6 c.1427+1G>C 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 5' splicing donor site. However, these predictions have yet to be confirmed by functional studies. The variant was absent in 251100 control chromosomes (gnomAD). To our knowledge, no occurrence of c.1427+1G>C in individuals affected with Neurodegeneration with Brain Iron Accumulation and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, and classified the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.