NM_002905.5(RDH5):c.382G>A (p.Asp128Asn) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 13, 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:: RCV002535735.3

Allele description [Variation Report for NM_002905.5(RDH5):c.382G>A (p.Asp128Asn)]

NM_002905.5(RDH5):c.382G>A (p.Asp128Asn)

Genes:

BLOC1S1-RDH5:BLOC1S1-RDH5 readthrough [Gene]
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.382G>A (p.Asp128Asn)

HGVS:

NC_000012.12:g.55721760G>A
NG_008606.1:g.6394G>A
NM_001199771.3:c.382G>A
NM_002905.4:c.382G>A
NM_002905.5:c.382G>AMANE SELECT
NP_001186700.1:p.Asp128Asn
NP_002896.2:p.Asp128Asn
NC_000012.11:g.56115544G>A
NM_001199771.1:c.382G>A
NM_002905.3:c.382G>A
NR_037658.1:n.441G>A

Protein change:

D128N

Links:

dbSNP: rs377029071

NCBI 1000 Genomes Browser:

rs377029071

Molecular consequence:

NM_001199771.3:c.382G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_002905.5:c.382G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_037658.1:n.441G>A - 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
SCV003520579	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 13, 2022)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 11675386, 17476461, 22736946, 22815624, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003520579

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 13, 2022)

germline

clinical testing

PubMed (5)
[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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

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

Fundus albipunctatus in a 6-year old girl due to compound heterozygous mutations in the RDH5 gene.

Iannaccone A, Tedesco SA, Gallaher KT, Yamamoto H, Charles S, Dryja TP.

Doc Ophthalmol. 2007 Sep;115(2):111-6. Epub 2007 May 3.

PubMed [citation]

PMID:: 17476461

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003520579.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects RDH5 function (PMID: 11675386). 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 RDH5 protein function. ClinVar contains an entry for this variant (Variation ID: 635161). This missense change has been observed in individual(s) with fundus albipunctatus or retinitis albescens (PMID: 17476461, 22736946, 22815624; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is present in population databases (rs377029071, gnomAD 0.002%). This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 128 of the RDH5 protein (p.Asp128Asn).

#	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: Sep 29, 2024

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