NM_206933.4(USH2A):c.2299del (p.Glu767fs) AND Retinitis pigmentosa 39

Germline classification:: Pathogenic (7 submissions)
Last evaluated:: Mar 30, 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:: RCV000191141.15

Allele description [Variation Report for NM_206933.4(USH2A):c.2299del (p.Glu767fs)]

NM_206933.4(USH2A):c.2299del (p.Glu767fs)

Gene:

USH2A:usherin [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

1q41

Genomic location:

Preferred name:

NM_206933.4(USH2A):c.2299del (p.Glu767fs)

Other names:

p.Glu767SerfsX21; NP_996816.3:p.(Glu767SerfsTer21)

HGVS:

NC_000001.11:g.216247095del
NG_009497.2:g.181354del
NG_076570.1:g.469del
NM_007123.6:c.2299del
NM_206933.4:c.2299delMANE SELECT
NP_009054.5:p.Glu767fs
NP_009054.6:p.Glu767fs
NP_996816.3:p.Glu767fs
NC_000001.10:g.216420437del
NC_000001.10:g.216420437delC
NG_009497.1:g.181302del
NM_007123.5:c.2299del
NM_007123.5:c.2299del
NM_007123.5:c.2299delG
NM_206933.2:c.2299delG
NM_206933.3:c.2299del
NM_206933.3:c.2299delG
NM_206933.4:c.2299delGMANE SELECT
c.2299delG

Note:

NCBI staff reviewed the sequence information reported in PubMed 9624053 Fig. 2B to determine the location of this allele on the current reference sequence.

Protein change:

E767fs

Links:

OMIM: 608400.0001; dbSNP: rs80338903

NCBI 1000 Genomes Browser:

rs80338903

Molecular consequence:

NM_007123.6:c.2299del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_206933.4:c.2299del - frameshift variant - [Sequence Ontology: SO:0001589]

Observations:

Condition(s)

Name:: Retinitis pigmentosa 39 (RP39)
Identifiers:: MONDO: MONDO:0013436; MedGen: C3151138; Orphanet: 791; OMIM: 613809

Recent activity

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exocyst complex component 1 isoform 2 [Rattus norvegicus]
exocyst complex component 1 isoform 2 [Rattus norvegicus]
gi|2191823158|ref|NP_001388261.1|

Protein
PREDICTED: Homo sapiens serine incorporator 5 (SERINC5), transcript variant X3, ...
PREDICTED: Homo sapiens serine incorporator 5 (SERINC5), transcript variant X3, mRNA
gi|2217355471|ref|XM_047417080.1|

Nucleotide
cytochrome c oxidase subunit I, partial (mitochondrion) [Oporornis agilis]
cytochrome c oxidase subunit I, partial (mitochondrion) [Oporornis agilis]
gi|2412883288|gb|WAO23895.1|

Protein
LOC127828899 [Homo sapiens]
LOC127828899 [Homo sapiens]
Gene ID:127828899

Gene
DBIP1 DBI pseudogene 1 [Homo sapiens]
DBIP1 DBI pseudogene 1 [Homo sapiens]
Gene ID:1624

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000245550	Baylor Genetics - Adult_WES	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Mar 30, 2024)	unknown	clinical testing	PubMed (2) [See all records that cite these PMIDs] 25741868, 26633545
SCV000490146	Counsyl	no assertion criteria provided	Pathogenic (Aug 18, 2016)	unknown	clinical testing	PubMed (2) [See all records that cite these PMIDs] 24607488, 10909849
SCV000804740	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	no assertion criteria provided	Pathogenic (Sep 1, 2016)	unknown	clinical testing
SCV001573518	Ocular Genomics Institute, Massachusetts Eye and Ear	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Apr 8, 2021)	germline	research	PubMed (10) [See all records that cite these PMIDs] 28041643, 20301515, 25649381, 25404053, 25097241, 24944099, 24607488, 20145675, 12525556, 25741868
SCV001760022	Genomics England Pilot Project, Genomics England	criteria provided, single submitter (ACGS Guidelines, 2016)	Pathogenic	germline	clinical testing	Citation Link,
SCV002521582	3billion	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (May 22, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004182441	Genome-Nilou Lab	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Nov 4, 2023)	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	germline	no	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	yes	1	not provided	not provided	not provided	not provided	clinical testing
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, research

Citations

PubMed

Molecular diagnostic experience of whole-exome sequencing in adult patients.

Posey JE, Rosenfeld JA, James RA, Bainbridge M, Niu Z, Wang X, Dhar S, Wiszniewski W, Akdemir ZH, Gambin T, Xia F, Person RE, Walkiewicz M, Shaw CA, Sutton VR, Beaudet AL, Muzny D, Eng CM, Yang Y, Gibbs RA, Lupski JR, Boerwinkle E, et al.

Genet Med. 2016 Jul;18(7):678-85. doi: 10.1038/gim.2015.142. Epub 2015 Dec 3.

PubMed [citation]

PMID:: 26633545
PMCID:: PMC4892996

Identification of novel USH2A mutations: implications for the structure of USH2A protein.

Dreyer B, Tranebjaerg L, Rosenberg T, Weston MD, Kimberling WJ, Nilssen O.

Eur J Hum Genet. 2000 Jul;8(7):500-6.

PubMed [citation]

PMID:: 10909849

See all PubMed Citations (12)

Details of each submission

From Baylor Genetics - Adult_WES, SCV000245550.2

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

#	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 Counsyl, SCV000490146.2

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

#	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 Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+, SCV000804740.2

#	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	unknown	yes	not provided	not provided	not provided		1	not provided	not provided	not provided

From Ocular Genomics Institute, Massachusetts Eye and Ear, SCV001573518.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	research	PubMed (10)

Description

The USH2A c.2299del 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, PP3. 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

From Genomics England Pilot Project, Genomics England, SCV001760022.1

#	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	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From 3billion, SCV002521582.1

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

Description

The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.070%). Frameshift: predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant. The variant has been reported at least twice as pathogenic with clinical assertions and evidence for the classification (ClinVar ID: VCV000002351). 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 Genome-Nilou Lab, SCV004182441.1

#	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	no	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Nov 3, 2024

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