NM_004183.4(BEST1):c.26T>G (p.Val9Gly) AND Vitelliform macular dystrophy type 2

Clinical significance:Likely pathogenic (Last evaluated: Sep 11, 2017)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000664327.1

Allele description [Variation Report for NM_004183.4(BEST1):c.26T>G (p.Val9Gly)]

NM_004183.4(BEST1):c.26T>G (p.Val9Gly)

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.26T>G (p.Val9Gly)
HGVS:
  • NC_000011.10:g.61951832T>G
  • NG_009033.1:g.6949T>G
  • NM_001139443.2:c.-29+1405T>G
  • NM_001300786.2:c.-29+1405T>G
  • NM_001300787.2:c.-29+1405T>G
  • NM_001363592.1:c.26T>G
  • NM_004183.4:c.26T>GMANE SELECT
  • NP_001350521.1:p.Val9Gly
  • NP_004174.1:p.Val9Gly
  • NC_000011.9:g.61719304T>G
  • NM_004183.3:c.26T>G
  • NR_134580.2:n.139T>G
Protein change:
V9G
Links:
dbSNP: rs281865205
NCBI 1000 Genomes Browser:
rs281865205
Molecular consequence:
  • NM_001139443.2:c.-29+1405T>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001300786.2:c.-29+1405T>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001300787.2:c.-29+1405T>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001363592.1:c.26T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_004183.4:c.26T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NR_134580.2:n.139T>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
Observations:
1

Condition(s)

Name:
Vitelliform macular dystrophy type 2 (VMD2)
Synonyms:
VITELLIFORM MACULAR DYSTROPHY, EARLY-ONSET; VITELLIFORM MACULAR DYSTROPHY, JUVENILE-ONSET; Best disease; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0007931; MedGen: C2745945; Orphanet: 1243; OMIM: 153700

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000599452MAGI'S LAB - Medical Genetics Laboratory, MAGI GROUPcriteria provided, single submitter
Likely pathogenic
(Sep 11, 2017)
paternalclinical testing

PubMed (1)
[See all records that cite this PMID]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedpaternalyes1not providednot providednot providednot providedclinical testing

Citations

PubMed

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 MAGI'S LAB - Medical Genetics Laboratory, MAGI GROUP, SCV000599452.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
11not providednot providedclinical testing PubMed (1)

Description

The variation c.26T>G, p.(Val9Gly) found in a patient affected by Best vitelliform macular dystrophy (BVMD) is located in a mutational hot spot, i.e. is a novel missense change at an amino acid residue where different missense changes such as p.(Val9Ala) (Petrukhin et al., 1998; Ponjavic et al., 1999), p.(Val9Met) (Marquardt et al., 1998), p.(Val9Glu) (Maia-Lopes et al., 2008) and p.(Val9Leu) (Kinnick et al., 2011) variants have been associated with BVMD before. Application of ACMG guidelines: PM1 Located in a mutational hot spot and/or critical and well-established functional domain (e.g., active site of an enzyme) without benign variation PM2 Absent from controls (or at extremely low frequency if recessive) (table 6) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium PM5 Novel missense change at an amino acid residue where a different missense change determined to be pathogenic has been seen before Example: Arg156His is pathogenic; now you observe Arg156Cys PP2 Missense variant in a gene that has a low rate of benign missense variation and in which missense variants are a common mechanism of disease PP3 Multiple lines of computational evidence support a deleterious effect on the gene or gene product (conservation, evolutionary, splicing impact, etc.) PP4 Patient’s phenotype or family history is highly specific for a disease with a single genetic etiology Likely pathogenic >=3 Moderate (PM1-PM6) OR 2 Moderate (PM1-PM6) AND >= 2 supporting (PP1-PP5)

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1paternalyesnot providednot providednot provided1not providednot providednot provided

Last Updated: May 11, 2020

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