Submissions for variant NM_207352.4(CYP4V2):c.1091-2A>G (rs199476183)

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Clinical Services Laboratory,Illumina	RCV000002275	SCV000448857	pathogenic	Bietti crystalline corneoretinal dystrophy	2017-04-27	criteria provided, single submitter	clinical testing	The CYP4V2 c.1091-2A>G variant occurs in a canonical splice site (acceptor) and is therefore predicted to disrupt or distort the normal gene product. Across a selection of available literature, the c.1091-2A>G variant has been identified in 30 individuals with retinal atrophy, Bietti crystalline dystrophy, or retinitis pigmentosa, including in a homozygous state in five individuals and in a compound heterozygous state in 25 individuals. In addition, it was reported in a heterozygous state in five unaffected family members (Li et al. 2004; Xiao et al. 2011; Wang et al. 2012; Fu et al. 2013; Meng et al. 2014). The c.1091-2A>G variant was absent from 196 controls and is reported at a frequency of 0.00035 in the East Asian population of the Exome Aggregation Consortium. Based on the potential impact of splice acceptor variants and evidence from the literature, the c.1091-2A>G variant is classified as pathogenic for Bietti crystalline dystrophy. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Ocular Genomics Institute, Massachusetts Eye and Ear	RCV000002275	SCV001573350	pathogenic	Bietti crystalline corneoretinal dystrophy	2021-04-08	criteria provided, single submitter	research	The CYP4V2 c.1091-2A>G variant was identified in an individual with retinitis pigmentosa with a presumed recessive inheritance pattern. Through a review of available evidence we were able to apply the following criteria: PVS1, PM2, PM3. Based on this evidence we have classified this variant as Pathogenic.
OMIM	RCV000002275	SCV000022433	pathogenic	Bietti crystalline corneoretinal dystrophy	2013-06-14	no assertion criteria provided	literature only
GeneReviews	RCV000002275	SCV000058224	pathologic	Bietti crystalline corneoretinal dystrophy	2012-04-12	no assertion criteria provided	curation	Converted during submission to Pathogenic.