Submissions for variant NM_002334.4(LRP4):c.3620A>G (p.Asn1207Ser)

gnomAD frequency: 0.00086  dbSNP: rs151234321

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000393021	SCV000340290	uncertain significance	not provided	2016-04-05	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000394052	SCV000372170	uncertain significance	Cenani-Lenz syndactyly syndrome	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001087525	SCV000765674	likely benign	Cenani-Lenz syndactyly syndrome; Sclerosteosis 2; Congenital myasthenic syndrome 17	2025-02-01	criteria provided, single submitter	clinical testing
Johns Hopkins Genomics, Johns Hopkins University	RCV000393021	SCV001711956	likely benign	not provided	2021-05-24	criteria provided, single submitter	clinical testing
GeneDx	RCV000393021	SCV001772345	likely benign	not provided	2021-09-07	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV004701383	SCV005202774	likely benign	not specified	2024-07-26	criteria provided, single submitter	clinical testing	Variant summary: LRP4 c.3620A>G (p.Asn1207Ser) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00094 in 251434 control chromosomes, predominantly at a frequency of 0.0017 within the Non-Finnish European subpopulation in the gnomAD database, including one homozygote. This frequency is not significantly higher than estimated for a pathogenic variant in LRP4 causing LRP4-Related Disorders, allowing no conclusion about variant significance. To our knowledge, no occurrence of c.3620A>G in individuals affected with LRP4-Related Disorders and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 286738). Based on the evidence outlined above, the variant was classified as likely benign.
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000393021	SCV001926685	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000393021	SCV001964973	likely benign	not provided		no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004543088	SCV004782594	likely benign	LRP4-related disorder	2022-12-14	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).