NM_000329.3(RPE65):c.893del (p.Lys298fs) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 16, 2024
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:: RCV001225799.7

Allele description [Variation Report for NM_000329.3(RPE65):c.893del (p.Lys298fs)]

NM_000329.3(RPE65):c.893del (p.Lys298fs)

Gene:

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

Variant type:

Deletion

Cytogenetic location:

1p31.3

Genomic location:

Preferred name:

NM_000329.3(RPE65):c.893del (p.Lys298fs)

Other names:

NM_000329.3(RPE65):c.893del; p.Lys298fs

HGVS:

NC_000001.11:g.68439051del
NG_008472.2:g.15913del
NM_000329.3:c.893delMANE SELECT
NP_000320.1:p.Lys298fs
NC_000001.10:g.68904730del
NC_000001.10:g.68904734del
NG_008472.1:g.15913del
NM_000329.2:c.889delA
NM_000329.2:c.893del
NM_000329.2:c.893delA
NM_000329.3:c.893delAMANE SELECT

Protein change:

K298fs

Links:

dbSNP: rs61752902

NCBI 1000 Genomes Browser:

rs61752902

Molecular consequence:

NM_000329.3:c.893del - frameshift variant - [Sequence Ontology: SO:0001589]

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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001398091	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 16, 2024)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 9326941, 9501220, 9843205, 18632300, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001398091

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 16, 2024)

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

Mutations in RPE65 cause autosomal recessive childhood-onset severe retinal dystrophy.

Gu SM, Thompson DA, Srikumari CR, Lorenz B, Finckh U, Nicoletti A, Murthy KR, Rathmann M, Kumaramanickavel G, Denton MJ, Gal A.

Nat Genet. 1997 Oct;17(2):194-7.

PubMed [citation]

PMID:: 9326941

Mutations in the RPE65 gene in patients with autosomal recessive retinitis pigmentosa or leber congenital amaurosis.

Morimura H, Fishman GA, Grover SA, Fulton AB, Berson EL, Dryja TP.

Proc Natl Acad Sci U S A. 1998 Mar 17;95(6):3088-93.

PubMed [citation]

PMID:: 9501220
PMCID:: PMC19699

See all PubMed Citations (5)

Details of each submission

From Invitae, SCV001398091.5

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

Description

This sequence change creates a premature translational stop signal (p.Lys298Serfs*27) in the RPE65 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in RPE65 are known to be pathogenic (PMID: 9326941, 9501220, 9843205, 18632300). This variant is present in population databases (rs757246161, gnomAD 0.006%). This premature translational stop signal has been observed in individual(s) with Leber congenital amaurosis (Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 372493). For these reasons, this variant has been classified as Pathogenic.

#	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: May 7, 2024

ClinVar

Relating variation to medicine