NM_206933.4(USH2A):c.14453C>T (p.Pro4818Leu) AND Usher syndrome type 2A

Germline classification:: Pathogenic/Likely pathogenic (3 submissions)
Last evaluated:: Nov 4, 2023
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:: RCV000986515.3

Allele description [Variation Report for NM_206933.4(USH2A):c.14453C>T (p.Pro4818Leu)]

NM_206933.4(USH2A):c.14453C>T (p.Pro4818Leu)

Gene:

USH2A:usherin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1q41

Genomic location:

Preferred name:

NM_206933.4(USH2A):c.14453C>T (p.Pro4818Leu)

HGVS:

NC_000001.11:g.215648657G>A
NG_009497.2:g.779792C>T
NM_206933.4:c.14453C>TMANE SELECT
NP_996816.3:p.Pro4818Leu
NC_000001.10:g.215821999G>A
NG_009497.1:g.779740C>T
NM_206933.2:c.14453C>T
NM_206933.3:c.14453C>T

Protein change:

P4818L

Links:

dbSNP: rs143344549

NCBI 1000 Genomes Browser:

rs143344549

Molecular consequence:

NM_206933.4:c.14453C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Usher syndrome type 2A
Synonyms:: USHER SYNDROME, TYPE IIA; RETINAL DISEASE IN USHER SYNDROME TYPE IIA, MODIFIER OF
Identifiers:: MONDO: MONDO:0010169; MedGen: C1848634; Orphanet: 231178; Orphanet: 886; OMIM: 276901

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
SCV001135530	Mendelics	criteria provided, single submitter (Mendelics Assertion Criteria 2017)	Likely pathogenic (May 28, 2019)	unknown	clinical testing	Citation Link,
SCV002766819	Victorian Clinical Genetics Services, Murdoch Childrens Research Institute See additional submitters Shariant Australia, Australian Genomics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Mar 31, 2022)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 22004887, 25472526, 29899460, 30081015, 32098976, 25741868
SCV004183066	Genome-Nilou Lab	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Nov 4, 2023)	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

SCV001135530

Mendelics

criteria provided, single submitter

(Mendelics Assertion Criteria 2017)

Likely pathogenic
(May 28, 2019)

unknown

clinical testing

Citation Link,

SCV002766819

Victorian Clinical Genetics Services, Murdoch Childrens Research Institute

See additional submitters

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Mar 31, 2022)

germline

clinical testing

PubMed (6)
[See all records that cite these PMIDs]

SCV004183066

Genome-Nilou Lab

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely 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	germline	unknown	not provided	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

Citations

PubMed

Mutational screening of the USH2A gene in Spanish USH patients reveals 23 novel pathogenic mutations.

Garcia-Garcia G, Aparisi MJ, Jaijo T, Rodrigo R, Leon AM, Avila-Fernandez A, Blanco-Kelly F, Bernal S, Navarro R, Diaz-Llopis M, Baiget M, Ayuso C, Millan JM, Aller E.

Orphanet J Rare Dis. 2011 Oct 17;6:65. doi: 10.1186/1750-1172-6-65.

PubMed [citation]

PMID:: 22004887
PMCID:: PMC3207874

Next-generation sequencing-based molecular diagnosis of 82 retinitis pigmentosa probands from Northern Ireland.

Zhao L, Wang F, Wang H, Li Y, Alexander S, Wang K, Willoughby CE, Zaneveld JE, Jiang L, Soens ZT, Earle P, Simpson D, Silvestri G, Chen R.

Hum Genet. 2015 Feb;134(2):217-30. doi: 10.1007/s00439-014-1512-7. Epub 2014 Dec 4.

PubMed [citation]

PMID:: 25472526
PMCID:: PMC4347882

See all PubMed Citations (6)

Details of each submission

From Mendelics, SCV001135530.1

#	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	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Victorian Clinical Genetics Services, Murdoch Childrens Research Institute, SCV002766819.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with retinitis pigmentosa 39 (MIM#613809) and type 2A Usher syndrome (MIM#276901). (I) 0106 - This gene is associated with autosomal recessive disease. (I) 0200 - Variant is predicted to result in a missense amino acid change from proline to leucine. (I) 0252 - This variant is homozygous. (I) 0304 - Variant is present in gnomAD <0.01 for a recessive condition (v3: 17 heterozygotes, 0 homozygotes). (SP) 0501 - Missense variant consistently predicted to be damaging by multiple in silico tools or highly conserved with a major amino acid change. (SP) 0604 - Variant is not located in an established domain, motif, hotspot or informative constraint region. (I) 0705 - No comparable missense variants have previous evidence for pathogenicity. (I) 0801 - This variant has strong previous evidence of pathogenicity in unrelated individuals. It has been reported in many individuals with autosomal recessive retinitis pigmentosa or Usher syndrome (PMIDs: 22004887, 25472526, 29899460, 30081015, 32098976). It has also been reported as likely pathogenic/pathogenic in ClinVar and Deafness Variation Database. (SP) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign

#	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

From Genome-Nilou Lab, SCV004183066.1

#	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: Mar 16, 2024

ClinVar

Relating variation to medicine