Submissions for variant NM_030787.4(CFHR5):c.1541T>G (p.Met514Arg)

dbSNP: rs141321678

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000890302	SCV001034036	benign	not provided	2023-12-21	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001099526	SCV001255990	uncertain significance	CFH-Related Dense Deposit Disease / Membranoproliferative Glomerulonephritis Type II	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). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV002294404	SCV002587658	likely benign	Atypical hemolytic-uremic syndrome	2020-07-13	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003994148	SCV004813281	likely benign	not specified	2024-02-16	criteria provided, single submitter	clinical testing	Variant summary: CFHR5 c.1541T>G (p.Met514Arg) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.0012 in 250066 control chromosomes, predominantly at a frequency of 0.0022 within the South Asian subpopulation in the gnomAD database. c.1541T>G has been reported in the literature in at least one individual affected with Haemolytic uraemic syndrome (Monteferrante_2007). The report does not provide unequivocal conclusions about association of the variant with CFHR5 Deficiency. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication have been ascertained in the context of this evaluation (PMID: 17000000). ClinVar contains an entry for this variant (Variation ID: 717499). Based on the evidence outlined above, the variant was classified as likely benign.
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000890302	SCV001955924	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000890302	SCV001964206	uncertain significance	not provided		no assertion criteria provided	clinical testing