NM_000329.3(RPE65):c.1418T>A (p.Val473Asp) AND multiple conditions

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Aug 20, 2020
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:: RCV001257424.1

Allele description [Variation Report for NM_000329.3(RPE65):c.1418T>A (p.Val473Asp)]

NM_000329.3(RPE65):c.1418T>A (p.Val473Asp)

Gene:

RPE65:retinoid isomerohydrolase RPE65 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1p31.3

Genomic location:

Preferred name:

NM_000329.3(RPE65):c.1418T>A (p.Val473Asp)

Other names:

NM_000329.3(RPE65):c.1418T>A

HGVS:

NC_000001.11:g.68431097A>T
NG_008472.2:g.23863T>A
NM_000329.3:c.1418T>AMANE SELECT
NP_000320.1:p.Val473Asp
NC_000001.10:g.68896780A>T
NG_008472.1:g.23863T>A
NM_000329.2:c.1418T>A
Q16518:p.Val473Asp

Protein change:

V473D

Links:

UniProtKB: Q16518#VAR_060823; dbSNP: rs62637007

NCBI 1000 Genomes Browser:

rs62637007

Molecular consequence:

NM_000329.3:c.1418T>A - missense variant - [Sequence Ontology: SO:0001583]

Functional consequence:

Unknown function

Observations:

Condition(s)

Name:: Leber congenital amaurosis 2 (LCA2)
Synonyms:: AMAUROSIS CONGENITA OF LEBER II; Amaurosis congenita of Leber, type 2; RPE65-Related Leber Congenital Amaurosis
Identifiers:: MONDO: MONDO:0008765; MedGen: C1859844; Orphanet: 65; OMIM: 204100

Name:: Retinitis pigmentosa 20 (RP20)
Synonyms:: RP 20
Identifiers:: MONDO: MONDO:0013425; MedGen: C3151086; Orphanet: 791; OMIM: 613794

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001430890	Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Aug 20, 2020)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001430890

Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Aug 20, 2020)

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
Muslim	germline	yes	1	not provided	not provided	not provided	not provided	clinical 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 Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics, SCV001430890.1

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

Description

A homozygous missense variation in exon 13 of the RPE65 gene that results in the amino acid substitution of Aspartic acid for Valine at codon 473 was detected. The observed variant c.1418T>A (p.Val473Asp) lies in the retinal pigment epithelial membrane protein domain of the RPE65 protein (Morimura et al. 1998) and has previously been reported in homozygous state in a patient affected with leber congenital amaurosis. The variant has not been reported in the 1000 genomes and gnomAD databases. The in silico prediction of the variant are probably damaging by PolyPhen-2 (HumDiv) and damaging by SIFT, LRT and MutationTaster2. The reference codon is conserved across species. In summary, the variant meets our criteria to be classified as likely pathogenic.

#	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		1	not provided	not provided	not provided

Last Updated: Apr 6, 2024

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