NM_002905.5(RDH5):c.712G>T (p.Gly238Trp) AND Pigmentary retinal dystrophy

Germline classification:: Pathogenic (5 submissions)
Last evaluated:: May 2, 2024
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:: RCV000988861.9

Allele description [Variation Report for NM_002905.5(RDH5):c.712G>T (p.Gly238Trp)]

NM_002905.5(RDH5):c.712G>T (p.Gly238Trp)

Genes:

BLOC1S1-RDH5:BLOC1S1-RDH5 readthrough [Gene]
CD63:CD63 molecule [Gene - OMIM - HGNC]
RDH5:retinol dehydrogenase 5 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

12q13.2

Genomic location:

Preferred name:

NM_002905.5(RDH5):c.712G>T (p.Gly238Trp)

Other names:

NP_002896.2:p.(Gly238Trp)

HGVS:

NC_000012.12:g.55724028G>T
NG_008347.1:g.10099C>A
NG_008606.1:g.8662G>T
NM_001199771.3:c.712G>T
NM_002905.5:c.712G>TMANE SELECT
NP_001186700.1:p.Gly238Trp
NP_002896.2:p.Gly238Trp
NC_000012.11:g.56117812G>T
NM_001199771.1:c.712G>T
NM_001199771.3:c.712G>T
NM_002905.3:c.712G>T
NM_002905.4:c.712G>T
NR_037658.1:n.771G>T
Q92781:p.Gly238Trp

Protein change:

G238W; GLY238TRP

Links:

UniProtKB: Q92781#VAR_009274; OMIM: 601617.0001; dbSNP: rs62638191

NCBI 1000 Genomes Browser:

rs62638191

Molecular consequence:

NM_001199771.3:c.712G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_002905.5:c.712G>T - missense variant - [Sequence Ontology: SO:0001583]
NR_037658.1:n.771G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Observations:

Condition(s)

Name:: Pigmentary retinal dystrophy
Synonyms:: Fundus albipunctatus
Identifiers:: MONDO: MONDO:0007639; MedGen: C0311338; Orphanet: 227796; Orphanet: 52427; OMIM: 136880; Human Phenotype Ontology: HP:0030642

Recent activity

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UI-R-BS0-ami-c-11-0-UI.r1 UI-R-BS0 Rattus norvegicus cDNA clone UI-R-BS0-ami-c-1...
UI-R-BS0-ami-c-11-0-UI.r1 UI-R-BS0 Rattus norvegicus cDNA clone UI-R-BS0-ami-c-11-0-UI 5', mRNA sequence
gi|11674323|gnl|dbEST|7094036|gb|BF 3.1|

Nucleotide
ARL14 effector protein isoform X2 [Rattus norvegicus]
ARL14 effector protein isoform X2 [Rattus norvegicus]
gi|2678929237|ref|XP_063139777.1|

Protein
F-box only protein 9 [Rattus norvegicus]
F-box only protein 9 [Rattus norvegicus]
gi|58865572|ref|NP_001011998.1|

Protein
PREDICTED: Homo sapiens serine incorporator 5 (SERINC5), transcript variant X2, ...
PREDICTED: Homo sapiens serine incorporator 5 (SERINC5), transcript variant X2, mRNA
gi|2217355469|ref|XM_047417079.1|

Nucleotide
Hydrogenophaga pseudoflava strain B2 16S ribosomal RNA gene, partial sequence
Hydrogenophaga pseudoflava strain B2 16S ribosomal RNA gene, partial sequence
gi|1321357987|gb|MG757547.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001138753	Mendelics	criteria provided, single submitter (Mendelics Assertion Criteria 2017)	Pathogenic (May 28, 2019)	unknown	clinical testing	Citation Link,
SCV001161236	Sharon lab, Hadassah-Hebrew University Medical Center	no assertion criteria provided	Pathogenic (Jun 23, 2019)	inherited	research
SCV002019654	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Sep 18, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002521584	3billion	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (May 22, 2022)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 10369264, 11675386, 10617778, 25741868
SCV005045622	Clinical Genetics and Genomics, Karolinska University Hospital	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (May 2, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	inherited	yes	not provided	not provided	not provided	not provided	not provided	research
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
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

Citations

PubMed

Mutations in the gene encoding 11-cis retinol dehydrogenase cause delayed dark adaptation and fundus albipunctatus.

Yamamoto H, Simon A, Eriksson U, Harris E, Berson EL, Dryja TP.

Nat Genet. 1999 Jun;22(2):188-91.

PubMed [citation]

PMID:: 10369264

Biochemical defects in 11-cis-retinol dehydrogenase mutants associated with fundus albipunctatus.

Lidén M, Romert A, Tryggvason K, Persson B, Eriksson U.

J Biol Chem. 2001 Dec 28;276(52):49251-7. Epub 2001 Oct 23.

PubMed [citation]

PMID:: 11675386

See all PubMed Citations (4)

Details of each submission

From Mendelics, SCV001138753.1

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

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

From Sharon lab, Hadassah-Hebrew University Medical Center, SCV001161236.1

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

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

From Revvity Omics, Revvity, SCV002019654.3

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

#	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, SCV002521584.1

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

Description

The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.021%). Functional studies provide strong evidence of the variant having a damaging effect on the gene or gene product (PMID:11675386). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.92; 3Cnet: 0.72). Same nucleotide change resulting in same amino acid change has been previously reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000008003). The variant has been reported to co-segregate with the disease in at least one similarly affected relative/individual in the same family or similarly affected unrelated family (PMID:10369264, 10617778). Therefore, this variant is classified as 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

From Clinical Genetics and Genomics, Karolinska University Hospital, SCV005045622.1

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

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

Last Updated: Nov 3, 2024

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