Submissions for variant NM_001006658.3(CR2):c.524C>T (p.Pro175Leu)

dbSNP: rs75282758

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000455760	SCV000538736	uncertain significance	not specified	2016-03-28	criteria provided, single submitter	clinical testing	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: 0.7% in East asian in ExAC with 2 homozygotes and 0.58% in european with 1 homozygote. Reported in 1/36 patients with hemolytic syndrome who also carried a c.1160-2A>G variant in CFH (Bu 2014). However, even the association gene-disease is not that strong (moderate).
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000658540	SCV000603221	likely benign	not provided	2023-08-15	criteria provided, single submitter	clinical testing
Invitae	RCV001083719	SCV000652490	likely benign	Immunodeficiency, common variable, 7	2024-01-31	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000658540	SCV000780315	likely benign	not provided	2023-09-01	criteria provided, single submitter	clinical testing	CR2: BP4, BS2
Mayo Clinic Laboratories, Mayo Clinic	RCV000658540	SCV001713935	uncertain significance	not provided	2019-11-18	criteria provided, single submitter	clinical testing
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV002056686	SCV002496081	uncertain significance	Systemic lupus erythematosus, susceptibility to, 9; Immunodeficiency, common variable, 7	2021-03-30	criteria provided, single submitter	clinical testing	CR2 NM_001006658.2 exon 3 p.Pro175Leu (c.524C>T): This variant has been reported in the literature in 1 individual with atypical hemolytic uremic syndrome (aHUS) (Bu 2014 PMID:24029428). This variant is present in 0.6% (410/68028) of European alleles including 1 homozygote in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/1-207468605-C-T?dataset=gnomad_r3). This variant is present in ClinVar, with classifications ranging from Variant of Uncertain Significance to Likely Benign (Variation ID:402563). Evolutionary conservation and computational predictive tools suggest that this variant may not impact the protein. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
GeneDx	RCV000658540	SCV004031794	uncertain significance	not provided	2023-08-26	criteria provided, single submitter	clinical testing	Observed in one individual from a cohort of patients with atypical hemolytic uremic syndrome and this individual also possessed a variant in another gene (Bu et al., 2014); 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: 34426522, 24029428)
PreventionGenetics, part of Exact Sciences	RCV003912788	SCV004731511	likely benign	CR2-related condition	2020-05-29	criteria provided, single submitter	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).