Submissions for variant NM_002335.4(LRP5):c.346G>A (p.Asp116Asn)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Neuberg Centre For Genomic Medicine, NCGM	RCV004785819	SCV005400873	uncertain significance	Osteoporosis with pseudoglioma	2023-06-22	criteria provided, single submitter	clinical testing	The observed missense c.346G>A(p.Asp116Asn) variant in LRP5 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This variant is reported with the allele frequency of 0.0008% in the gnomAD Exomes. The amino acid Asp at position 116 is changed to a Asn changing protein sequence and it might alter its composition and physico-chemical properties. The amino acid change p.Asp116Asn in LRP5 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. Multiple lines of computational evidence (Polyphen - Damaging, SIFT - Damaging, and MutationTaster - Disease causing) predict a damaging effect on protein structure and function for this variant. For these reasons, this variant has been classified as Uncertain Significance.
GeneDx	RCV005001477	SCV005626551	uncertain significance	not provided	2024-07-09	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 29055141)