Submissions for variant NM_003366.4(UQCRC2):c.757_766+3del

dbSNP: rs745553184

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000494594	SCV000583070	pathogenic	not provided	2017-05-22	criteria provided, single submitter	clinical testing	The c.757_766+3del13 variant in the UQCRC2 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 that spans the intron/exon boundary. The c.757_766+3del13 variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). We interpret c.757_766+3del13 as a pathogenic variant.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000494594	SCV002172111	uncertain significance	not provided	2021-10-11	criteria provided, single submitter	clinical testing	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: 430296). This variant has been observed in individual(s) with mitochondrial complex III deficiency (external communication). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant results in the deletion of part of exon 9 of the UQCRC2 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), however the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in UQCRC2 cause disease. 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.