NM_207352.4(CYP4V2):c.367A>G (p.Met123Val) AND Bietti crystalline corneoretinal dystrophy

This record was updated by the submitter. Please see the current version.

Germline classification:: Uncertain significance (4 submissions)
Last evaluated:: Sep 1, 2022
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000032541.11

Allele description

NM_207352.4(CYP4V2):c.367A>G (p.Met123Val)

Gene:

CYP4V2:cytochrome P450 family 4 subfamily V member 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

4q35.1

Genomic location:

Preferred name:

NM_207352.4(CYP4V2):c.367A>G (p.Met123Val)

HGVS:

NC_000004.12:g.186196042A>G
NG_007965.1:g.9523A>G
NM_207352.4:c.367A>GMANE SELECT
NP_997235.3:p.Met123Val
NC_000004.11:g.187117196A>G
NM_207352.3:c.367A>G
Q6ZWL3:p.Met123Val

Nucleotide change:

c.671A>G

Protein change:

M123V

Links:

UniProtKB: Q6ZWL3#VAR_023088; dbSNP: rs149684063

NCBI 1000 Genomes Browser:

rs149684063

Molecular consequence:

NM_207352.4:c.367A>G - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Bietti crystalline corneoretinal dystrophy (BCD)
Synonyms:: BIETTI TAPETORETINAL DEGENERATION WITH MARGINAL CORNEAL DYSTROPHY; Bietti Crystalline Dystrophy
Identifiers:: MONDO: MONDO:0008865; MedGen: C1859486; OMIM: 210370

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000056208	GeneReviews	no assertion criteria provided	pathologic (Apr 12, 2012)	not provided	curation
SCV000267285	Soonchunhyang University Bucheon Hospital, Soonchunhyang University Medical Center	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Mar 18, 2016)	germline	reference population	PubMed (2) [See all records that cite these PMIDs] 15042513, 25741868
SCV000448827	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification Criteria 09 May 2019)	Uncertain significance (Apr 27, 2017)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link,
SCV002572707	3billion	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Sep 1, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 15042513, 25741868

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Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	1	not provided	not provided	1	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	not provided	not provided	not provided	not provided	not provided	not provided	not provided	curation
East Asian	germline	unknown	1	not provided	not provided	not provided	not provided	reference population

Citations

PubMed

Bietti crystalline corneoretinal dystrophy is caused by mutations in the novel gene CYP4V2.

Li A, Jiao X, Munier FL, Schorderet DF, Yao W, Iwata F, Hayakawa M, Kanai A, Shy Chen M, Alan Lewis R, Heckenlively J, Weleber RG, Traboulsi EI, Zhang Q, Xiao X, Kaiser-Kupfer M, Sergeev YV, Hejtmancik JF.

Am J Hum Genet. 2004 May;74(5):817-26. Epub 2004 Mar 23.

PubMed [citation]

PMID:: 15042513
PMCID:: PMC1181977

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From GeneReviews, SCV000056208.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	curation	not provided

Description

Converted during submission to Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	not provided	not provided	not provided	not provided	Assert pathogenicity		not provided	not provided	not provided	not provided

From Soonchunhyang University Bucheon Hospital, Soonchunhyang University Medical Center, SCV000267285.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	East Asian	1	not provided	not provided	reference population	PubMed (2)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		1	not provided	not provided	not provided

From Illumina Laboratory Services, Illumina, SCV000448827.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

The CYP4V2 c.367A>G (p.Met123Val) missense variant has been reported in a compound heterozygous state in one individual with Bietti crystalline dystrophy (Li et al. 2004). The p.Met123Val variant was absent from 100 controls but is reported at a frequency of 0.00496 in the East Asian population of the 1000 Genomes Project. The evidence for this variant is limited. The p.Met123Val variant is therefore classified as a variant of unknown significance but suspicious for pathogenicity for Bietti crystalline dystrophy. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From 3billion, SCV002572707.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (2)

Description

The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.074%). Same nucleotide change resulting in same amino acid change has been previously reported to be associated with CYP4V2-related disorder (PMID: 15042513). However, the evidence of pathogenicity is insufficient at this time. Therefore, this variant is classified as uncertain significance according to the recommendation of ACMG/AMP guideline.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	1	not provided	not provided		1	not provided	not provided	not provided

Last Updated: Jan 19, 2025

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