Submissions for variant NM_001029896.2(WDR45):c.436+5G>A

dbSNP: rs1057521933

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000427230	SCV000525120	likely pathogenic	not provided	2016-09-19	criteria provided, single submitter	clinical testing	The c.439+5G>A variant in the WDR45 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This variant reduces the quality of the splice donor site in intron 7, and is expected to cause abnormal gene splicing. The c.439+5G>A variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Based on the available information, c.439+5G>A is a strong candidate for a pathogenic variant.
Invitae	RCV001303363	SCV001492605	uncertain significance	Neurodegeneration with brain iron accumulation 5	2022-08-10	criteria provided, single submitter	clinical testing	This variant is not present in population databases (gnomAD no frequency). This sequence change falls in intron 7 of the WDR45 gene. It does not directly change the encoded amino acid sequence of the WDR45 protein. It affects a nucleotide within the consensus splice site. This variant has not been reported in the literature in individuals affected with WDR45-related conditions. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 384351).