NM_004183.4(BEST1):c.682G>C (p.Asp228His) AND Autosomal dominant vitreoretinochoroidopathy

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: May 22, 2022
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV002250720.1

Allele description [Variation Report for NM_004183.4(BEST1):c.682G>C (p.Asp228His)]

NM_004183.4(BEST1):c.682G>C (p.Asp228His)

Gene:

BEST1:bestrophin 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

11q12.3

Genomic location:

Preferred name:

NM_004183.4(BEST1):c.682G>C (p.Asp228His)

HGVS:

NC_000011.10:g.61957432G>C
NG_009033.1:g.12549G>C
NM_001139443.2:c.502G>C
NM_001300786.2:c.502G>C
NM_001300787.2:c.502G>C
NM_001363591.2:c.364G>C
NM_001363592.1:c.682G>C
NM_001363593.2:c.-494G>C
NM_004183.4:c.682G>CMANE SELECT
NP_001132915.1:p.Asp168His
NP_001287715.1:p.Asp168His
NP_001287716.1:p.Asp168His
NP_001350520.1:p.Asp122His
NP_001350521.1:p.Asp228His
NP_004174.1:p.Asp228His
NC_000011.9:g.61724904G>C
NM_004183.3:c.682G>C
NR_134580.2:n.795G>C

Protein change:

D122H

Links:

dbSNP: rs267606676

NCBI 1000 Genomes Browser:

rs267606676

Molecular consequence:

NM_001363593.2:c.-494G>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001139443.2:c.502G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001300786.2:c.502G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001300787.2:c.502G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001363591.2:c.364G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001363592.1:c.682G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_004183.4:c.682G>C - missense variant - [Sequence Ontology: SO:0001583]
NR_134580.2:n.795G>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Observations:

Condition(s)

Name:: Autosomal dominant vitreoretinochoroidopathy
Synonyms:: VITREORETINOCHOROIDOPATHY WITH MICROCORNEA, GLAUCOMA, AND CATARACT; Vitreoretinochoroidopathy dominant; VRCP autosomal dominant; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0008662; MedGen: C3888099; Orphanet: 263347; Orphanet: 3086; OMIM: 193220

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002521563	3billion	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (May 22, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 25999674, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002521563

3billion

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(May 22, 2022)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

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

Citations

PubMed

The efficacy of microarray screening for autosomal recessive retinitis pigmentosa in routine clinical practice.

van Huet RA, Pierrache LH, Meester-Smoor MA, Klaver CC, van den Born LI, Hoyng CB, de Wijs IJ, Collin RW, Hoefsloot LH, Klevering BJ.

Mol Vis. 2015;21:461-76.

PubMed [citation]

PMID:: 25999674
PMCID:: PMC4415583

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 3billion, SCV002521563.1

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

Description

The variant is not observed in the gnomAD v2.1.1 dataset. The variant is located in a mutational hot spot and/or well-established functional domain in which established pathogenic variants have been reported. Missense changes are a common disease-causing mechanism. In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.99; 3Cnet: 0.99). Same nucleotide change resulting in same amino acid change has been previously reported to be associated with BEST1 related disorder (PMID: 25999674). Different missense changes at the same codon (p.Asp228Asn, p.Asp228Glu) have been reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000002748, VCV000522450). Therefore, this variant is classified as likely pathogenic 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: Feb 20, 2024

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