Submissions for variant NM_002335.4(LRP5):c.1413-7T>A

gnomAD frequency: 0.00077  dbSNP: rs141889567

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000579350	SCV000680930	uncertain significance	not provided	2024-05-29	criteria provided, single submitter	clinical testing	In silico analysis is inconclusive as to whether the variant alters gene splicing; in the absence of RNA/functional studies the actual effect of this sequence change is unknown; Has not been previously published as pathogenic or benign to our knowledge
Labcorp Genetics (formerly Invitae), Labcorp	RCV000579350	SCV001023114	likely benign	not provided	2024-01-25	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000579350	SCV001334458	uncertain significance	not provided	2020-02-01	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV001335928	SCV001529189	uncertain significance	Osteoporosis with pseudoglioma	2018-12-06	criteria provided, single submitter	clinical testing	This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Athena Diagnostics	RCV000579350	SCV002770692	uncertain significance	not provided	2021-12-07	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001701094	SCV003800907	benign	not specified	2023-01-06	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000579350	SCV004564972	uncertain significance	not provided	2023-09-08	criteria provided, single submitter	clinical testing	The LRP5 c.1413-7T>A variant (rs141889567), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 488970). This variant is found in the general population with an overall allele frequency of 0.08% (238/282,840 alleles, with one homozygote) in the Genome Aggregation Database. This is an intronic variant in a weakly conserved nucleotide, and computational analyses (Alamut v.2.11) predict that this variant may impact splicing by weakening the nearby canonical acceptor splice site. However, RNA studies would be required to confirm this. Given the lack of clinical and functional data, the significance of the c.1413-7T>A variant is uncertain at this time.
Mayo Clinic Laboratories, Mayo Clinic	RCV000579350	SCV005412391	uncertain significance	not provided	2024-08-14	criteria provided, single submitter	clinical testing	BS1
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000579350	SCV001797319	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV001701094	SCV001919809	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000579350	SCV001953304	likely benign	not provided		no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003905501	SCV004723394	likely benign	LRP5-related disorder	2021-01-19	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).