Submissions for variant NM_207352.4(CYP4V2):c.802-8_810delinsGC

dbSNP: rs207482233

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000032548	SCV000448843	pathogenic	Bietti crystalline corneoretinal dystrophy	2016-06-14	criteria provided, single submitter	clinical testing	The c.802-8_810delTCATACAGGTCATCGCTinsGC variant, also described in the literature as c.802-8_810delinsG, occurs in a canonical splice site (acceptor) and is therefore predicted to disrupt or distort the normal gene product. The c.802-8_810delTCATACAGGTCATCGCTinsGC variant is the most common variant associated with Bietti crystalline dystrophy in the Japanese and Chinese populations, accounting for up to 83% of disease alleles (Park et al. 2016). The variant has been reported in at least nine studies in which it is found in at least 130 patients including 64 in a homozygous state, 65 in a compound heterozygous state and one individual in a heterozygous state in whom a second allele has not been detected (Li et al. 2004; Wada et al. 2006; Lai et al. 2007; Xiao et al. 2011; Yin et al. 2014; Meng et al. 2014; Tian et al. 2015; Park et al. 2016; Astuti et al. 2016). The variant was absent from 146 controls but is reported at a frequency of 0.00496 in the East Asian population of the 1000 Genomes Project. Due to the potential impact of splice acceptor variants and the supporting evidence from the literature, the c.802-8_810delTCATACAGGTCATCGCTinsGC variant is classified as pathogenic for Bietti crystalline dystrophy.
Illumina Laboratory Services, Illumina	RCV000355196	SCV000448844	uncertain significance	Corneal Dystrophy, Recessive	2016-06-14	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000726829	SCV000703391	pathogenic	not provided	2016-11-18	criteria provided, single submitter	clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000032548	SCV000731492	pathogenic	Bietti crystalline corneoretinal dystrophy	2017-02-06	criteria provided, single submitter	clinical testing	The c.802-8_810delinsGC (NM_207352.3 c.802-8_810delinsGC) variant in CYP4V2 has been reported in over 60 homozygous and compound heterozygous individuals with B ietti crystalline dystrophy and related disorders and is the most common variant associated with this disease in East Asian populations (Wada 2005, Lin 2005, La i 2007, Yokoi 2010, Xiao 2011, Wang 2012, Chung 2013, Fu 2013, Yin 2014, Meng 20 14, Tian 2015, Astuti 2015, and Park 2016). This variant has also been reported as pathogenic in ClinVar (Variation ID#39271). This variant has been identified in 0.2% (16/8520) of East Asian chromosomes by chromosomes by the Exome Aggregat ion Consortium (ExAC, http://exac.broadinstitute.org). This variant alters the c anonical splice site, and therefore is expected to impact splicing and lead to a n absent or truncated protein. In summary, this variant meets criteria to be cla ssified as pathogenic for Bietti crystalline dystrophy and related disorders in an autosomal recessive manner based upon its biallelic occurrence in patients wi th this disease and predicted functional impact.
Blueprint Genetics	RCV001075704	SCV001241332	pathogenic	Retinal dystrophy	2019-04-23	criteria provided, single submitter	clinical testing
Ocular Genomics Institute, Massachusetts Eye and Ear	RCV000032548	SCV001573765	pathogenic	Bietti crystalline corneoretinal dystrophy	2021-04-08	criteria provided, single submitter	research	The CYP4V2 c.802-8_810delinsGC 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: PM2, PVS1, PM3. Based on this evidence we have classified this variant as Pathogenic.
Revvity Omics, Revvity	RCV000032548	SCV002018134	pathogenic	Bietti crystalline corneoretinal dystrophy	2020-02-05	criteria provided, single submitter	clinical testing
GeneDx	RCV000726829	SCV002107214	pathogenic	not provided	2022-03-14	criteria provided, single submitter	clinical testing	Canonical splice site variant expected to result in aberrant splicing, although in the absence of functional evidence the actual effect of this sequence change is unknown.; Reported as the most common pathogenic variant among individuals of East Asian background, accounting for 62.6% of pathogenic variants identified in one study (Zhang et al., 2018); Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 27658286, 25629076, 15042513, 23793346, 22693542, 15860296, 26865810, 24480711, 28848678, 16088246, 28763560, 30029497, 19508456, 30609409, 31054281, 31872526, 31960602, 33964374, 33857831, 33090715, 33306817, 33781268, 34068831, 30429639, 15937078)
GeneReviews	RCV000032548	SCV000056215	pathologic	Bietti crystalline corneoretinal dystrophy	2012-04-12	no assertion criteria provided	curation	Converted during submission to Pathogenic.
Department of Ophthalmology and Visual Sciences Kyoto University	RCV000032548	SCV000172674	pathogenic	Bietti crystalline corneoretinal dystrophy		no assertion criteria provided	not provided	Converted during submission to Pathogenic.
OMIM	RCV000032548	SCV000246149	pathogenic	Bietti crystalline corneoretinal dystrophy	2013-06-14	no assertion criteria provided	literature only