Submissions for variant NM_004525.3(LRP2):c.1176C>T (p.Gly392=)

gnomAD frequency: 0.00070  dbSNP: rs369145798

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000599575	SCV000710659	uncertain significance	not provided	2018-02-27	criteria provided, single submitter	clinical testing	The c.1176 C>T variant in the LRP2 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The c.1176 C>T variant is observed in 50/23996 (0.2%) alleles from individuals of African background, and no individuals were reported to be homozygous (Lek et al., 2016). The c.1176 C>T variant represents a synonymous amino acid substitution that occurs at a position that is not conserved across species. In silico splice prediction models predict that c.1176 C>T may create a new cryptic splice donor site upstream of the canonical splice donor site in intron 11. However, in the absence of RNA/functional studies, the actual effect of this sequence change in this individual is unknown. We interpret c.1176 C>T as a variant of uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000599575	SCV001728149	benign	not provided	2025-01-27	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001807302	SCV002055733	likely benign	Donnai-Barrow syndrome	2021-07-15	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV001807302	SCV005652274	likely benign	Donnai-Barrow syndrome	2024-04-23	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003915743	SCV004734345	likely benign	LRP2-related disorder	2023-08-16	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).