Submissions for variant NM_004525.3(LRP2):c.10906C>T (p.Arg3636Trp)

gnomAD frequency: 0.00009  dbSNP: rs747833963

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000345477	SCV000419054	uncertain significance	Donnai-Barrow syndrome	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001411742	SCV001613808	likely benign	not provided	2024-01-29	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000345477	SCV002054707	likely benign	Donnai-Barrow syndrome	2021-07-15	criteria provided, single submitter	clinical testing
Daryl Scott Lab, Baylor College of Medicine	RCV000345477	SCV002515353	uncertain significance	Donnai-Barrow syndrome	2022-02-01	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002521314	SCV003608287	uncertain significance	Inborn genetic diseases	2022-09-06	criteria provided, single submitter	clinical testing	The c.10906C>T (p.R3636W) alteration is located in exon 56 (coding exon 56) of the LRP2 gene. This alteration results from a C to T substitution at nucleotide position 10906, causing the arginine (R) at amino acid position 3636 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
PreventionGenetics, part of Exact Sciences	RCV004751477	SCV005345361	uncertain significance	LRP2-related disorder	2024-07-27	no assertion criteria provided	clinical testing	The LRP2 c.10906C>T variant is predicted to result in the amino acid substitution p.Arg3636Trp. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.025% of alleles in individuals of Latino descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.