Submissions for variant NM_004525.3(LRP2):c.6858T>A (p.Phe2286Leu)

gnomAD frequency: 0.00089  dbSNP: rs140918583

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000657956	SCV000779726	uncertain significance	not provided	2023-05-18	criteria provided, single submitter	clinical testing	Identified as a germline variant in two cousins with childhood cancers, although several other variants were also identified and proposed as candidates for the cancer predisposition in this family (Derpoorter et al., 2019); 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: 30350915)
Fulgent Genetics, Fulgent Genetics	RCV000765533	SCV000896848	uncertain significance	Donnai-Barrow syndrome	2018-10-31	criteria provided, single submitter	clinical testing
Invitae	RCV000657956	SCV001036219	likely benign	not provided	2024-01-31	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000657956	SCV001152549	uncertain significance	not provided	2023-12-01	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000765533	SCV001291497	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.
Genome-Nilou Lab	RCV000765533	SCV002055213	uncertain significance	Donnai-Barrow syndrome	2021-07-15	criteria provided, single submitter	clinical testing
New York Genome Center	RCV000765533	SCV002097685	uncertain significance	Donnai-Barrow syndrome	2020-07-10	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002534263	SCV003714486	likely benign	Inborn genetic diseases	2021-10-09	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
PreventionGenetics, part of Exact Sciences	RCV003980284	SCV004789747	uncertain significance	LRP2-related condition	2024-01-24	criteria provided, single submitter	clinical testing	The LRP2 c.6858T>A variant is predicted to result in the amino acid substitution p.Phe2286Leu. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.13% of alleles in individuals of Latino descent in gnomAD. Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Centre de Biologie Pathologie Génétique, Centre Hospitalier Universitaire de Lille	RCV001252552	SCV001428309	likely benign	Intellectual disability	2019-01-01	no assertion criteria provided	clinical testing