NM_004183.4(BEST1):c.905A>T (p.Asp302Val) AND not provided

Germline classification:: Likely pathogenic (2 submissions)
Last evaluated:: Jul 6, 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:: RCV000086195.7

Allele description [Variation Report for NM_004183.4(BEST1):c.905A>T (p.Asp302Val)]

NM_004183.4(BEST1):c.905A>T (p.Asp302Val)

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.905A>T (p.Asp302Val)

HGVS:

NC_000011.10:g.61959535A>T
NG_009033.1:g.14652A>T
NM_001139443.2:c.725A>T
NM_001300786.2:c.688-357A>T
NM_001300787.2:c.725A>T
NM_001363591.2:c.587A>T
NM_001363592.1:c.1108A>T
NM_001363593.2:c.-68A>T
NM_004183.4:c.905A>TMANE SELECT
NP_001132915.1:p.Asp242Val
NP_001287716.1:p.Asp242Val
NP_001350520.1:p.Asp196Val
NP_001350521.1:p.Met370Leu
NP_004174.1:p.Asp302Val
NC_000011.9:g.61727007A>T
NM_004183.3:c.905A>T
NR_134580.2:n.1221A>T
O76090:p.Asp302Val

Protein change:

D196V

Links:

UniProtKB: O76090#VAR_025748; dbSNP: rs281865263

NCBI 1000 Genomes Browser:

rs281865263

Molecular consequence:

NM_001363593.2:c.-68A>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001300786.2:c.688-357A>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001139443.2:c.725A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001300787.2:c.725A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001363591.2:c.587A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001363592.1:c.1108A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_004183.4:c.905A>T - missense variant - [Sequence Ontology: SO:0001583]
NR_134580.2:n.1221A>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000118339	Retina International	no classification provided	not provided	not provided	not provided
SCV002297815	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Jul 6, 2022)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 21269699, 28559085, 10798642, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000118339

Retina International

no classification provided

not provided

SCV002297815

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Jul 6, 2022)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

Description

http://phencode.bx.psu.edu/cgi-bin/phencode/phencode?build=hg19&id=RISN_VMD2:c.905A>T: SCV000118339

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
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	1	not provided	literature only

Citations

PubMed

Systematic screening of BEST1 and PRPH2 in juvenile and adult vitelliform macular dystrophies: a rationale for molecular analysis.

Meunier I, Sénéchal A, Dhaenens CM, Arndt C, Puech B, Defoort-Dhellemmes S, Manes G, Chazalette D, Mazoir E, Bocquet B, Hamel CP.

Ophthalmology. 2011 Jun;118(6):1130-6. doi: 10.1016/j.ophtha.2010.10.010. Epub 2011 Jan 26.

PubMed [citation]

PMID:: 21269699

Clinically Focused Molecular Investigation of 1000 Consecutive Families with Inherited Retinal Disease.

Stone EM, Andorf JL, Whitmore SS, DeLuca AP, Giacalone JC, Streb LM, Braun TA, Mullins RF, Scheetz TE, Sheffield VC, Tucker BA.

Ophthalmology. 2017 Sep;124(9):1314-1331. doi: 10.1016/j.ophtha.2017.04.008. Epub 2017 May 27.

PubMed [citation]

PMID:: 28559085
PMCID:: PMC5565704

See all PubMed Citations (4)

Details of each submission

From Retina International, SCV000118339.1

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

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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002297815.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Asp302 amino acid residue in BEST1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 21269699, 28559085). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt BEST1 protein function. ClinVar contains an entry for this variant (Variation ID: 99776). This missense change has been observed in individual(s) with BEST1-related conditions (PMID: 10798642). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces aspartic acid, which is acidic and polar, with valine, which is neutral and non-polar, at codon 302 of the BEST1 protein (p.Asp302Val).

#	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

Last Updated: Oct 8, 2024

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