NM_000329.3(RPE65):c.11+5G>A AND Retinitis pigmentosa 20

Germline classification:: Pathogenic/Likely pathogenic (4 submissions)
Last evaluated:: Apr 8, 2021
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:: RCV000678614.7

Allele description [Variation Report for NM_000329.3(RPE65):c.11+5G>A]

NM_000329.3(RPE65):c.11+5G>A

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.11+5G>A

HGVS:

NC_000001.11:g.68449890C>T
NG_008472.2:g.5070G>A
NM_000329.3:c.11+5G>AMANE SELECT
NC_000001.10:g.68915573C>T
NG_008472.1:g.5070G>A
NM_000329.2:c.11+5G>A

Nucleotide change:

IVS1, G-A, +5

Links:

OMIM: 180069.0010; dbSNP: rs61751276

NCBI 1000 Genomes Browser:

rs61751276

Molecular consequence:

NM_000329.3:c.11+5G>A - intron variant - [Sequence Ontology: SO:0001627]

Observations:

Condition(s)

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

Recent activity

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right-handed parallel beta-helix repeat-containing protein [Blautia pseudococcoi...
right-handed parallel beta-helix repeat-containing protein [Blautia pseudococcoides]
gi|1957932539|gnl|PRJNA680355|I5Q86 5|gb|QQQ92440.1|

Protein
PREDICTED: uncharacterized protein LOC107349325 [Acropora digitifera]
PREDICTED: uncharacterized protein LOC107349325 [Acropora digitifera]
gi|1005468063|ref|XP_015770945.1|

Protein
uncharacterized protein LOC5504114 [Nematostella vectensis]
uncharacterized protein LOC5504114 [Nematostella vectensis]
gi|156359994|ref|XP_001625047.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000044040	OMIM	no assertion criteria provided	Pathogenic (Sep 1, 2003)	germline	literature only	PubMed (2) [See all records that cite these PMIDs] 11786058, 12960219
SCV000804701	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	no assertion criteria provided	Likely pathogenic (Sep 1, 2016)	inherited	clinical testing
SCV001370364	Centre for Mendelian Genomics, University Medical Centre Ljubljana	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Jun 12, 2019)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001573683	Ocular Genomics Institute, Massachusetts Eye and Ear	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Apr 8, 2021)	germline	research	PubMed (9) [See all records that cite these PMIDs] 28041643, 25257057, 21211845, 20683928, 19854499, 11786058, 11462243, 9326941, 25741868

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	unknown	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	inherited	yes	1	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	research

Citations

PubMed

A Tyr368His RPE65 founder mutation is associated with variable expression and progression of early onset retinal dystrophy in 10 families of a genetically isolated population.

Yzer S, van den Born LI, Schuil J, Kroes HY, van Genderen MM, Boonstra FN, van den Helm B, Brunner HG, Koenekoop RK, Cremers FP.

J Med Genet. 2003 Sep;40(9):709-13. No abstract available.

PubMed [citation]

PMID:: 12960219
PMCID:: PMC1735582

Comprehensive Rare Variant Analysis via Whole-Genome Sequencing to Determine the Molecular Pathology of Inherited Retinal Disease.

Carss KJ, Arno G, Erwood M, Stephens J, Sanchis-Juan A, Hull S, Megy K, Grozeva D, Dewhurst E, Malka S, Plagnol V, Penkett C, Stirrups K, Rizzo R, Wright G, Josifova D, Bitner-Glindzicz M, Scott RH, Clement E, Allen L, Armstrong R, Brady AF, et al.

Am J Hum Genet. 2017 Jan 5;100(1):75-90. doi: 10.1016/j.ajhg.2016.12.003. Epub 2016 Dec 29.

PubMed [citation]

PMID:: 28041643
PMCID:: PMC5223092

See all PubMed Citations (10)

Details of each submission

From OMIM, SCV000044040.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (2)

Description

For discussion of the splice site mutation (IVS1+5G-A) in the RPE65 gene that was found in compound heterozygous state in 2 brothers with retinitis pigmentosa-20 (RP20; 613794) by Felius et al. (2002), see 180069.0009.

Felius et al. (2002) stated that the IVS1+5G-A splice site mutation was the most common of the known RPE65 mutations and that it occurred on at least 2 genetic backgrounds.

For discussion of a patient with Leber congenital amaurosis-2 (LCA2; 204100) reported by Yzer et al. (2003) who was compound heterozygous for IVS1+5G-A and Y368H in the RPE65 gene, see 180069.0009.

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

From Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+, SCV000804701.2

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

From Centre for Mendelian Genomics, University Medical Centre Ljubljana, SCV001370364.2

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

Description

This variant was classified as: Likely pathogenic. The following ACMG criteria were applied in classifying this variant: PS1,PM2,PM3,PP3.

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

From Ocular Genomics Institute, Massachusetts Eye and Ear, SCV001573683.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	research	PubMed (9)

Description

The RPE65 c.11+5G>A variant was identified in an individual with retinitis pigmentosa with a presumed recessive inheritance pattern. Through a review of available evidence we were able to apply the following criteria: PVS1, PM2, PM3, PP1-S, PP3, PM1. Based on this evidence we have classified this variant as 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		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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