Submissions for variant NM_000092.5(COL4A4):c.193-2A>C

dbSNP: rs2125038490

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001378541	SCV001576128	pathogenic	not provided	2021-02-08	criteria provided, single submitter	clinical testing	This sequence change affects an acceptor splice site in intron 4 of the COL4A4 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in COL4A4 are known to be pathogenic (PMID: 21196518, 24854265, 25307543). This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with clinical features of Alport syndrome (PMID: 31686460, Invitae). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. For these reasons, this variant has been classified as Pathogenic.
Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München	RCV002468634	SCV002765006	likely pathogenic	Benign familial hematuria	2022-08-01	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV005023126	SCV005653689	pathogenic	Autosomal recessive Alport syndrome; Hematuria, benign familial, 1	2024-05-31	criteria provided, single submitter	clinical testing