NM_206933.4(USH2A):c.13374del (p.Glu4458fs) AND not provided

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Sep 11, 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:: RCV000493634.9

Allele description [Variation Report for NM_206933.4(USH2A):c.13374del (p.Glu4458fs)]

NM_206933.4(USH2A):c.13374del (p.Glu4458fs)

Gene:

USH2A:usherin [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

1q41

Genomic location:

Preferred name:

NM_206933.4(USH2A):c.13374del (p.Glu4458fs)

HGVS:

NC_000001.10:g.215847879del
NC_000001.11:g.215674538del
NG_009497.2:g.753912del
NM_206933.4:c.13374delMANE SELECT
NP_996816.3:p.Glu4458fs
NC_000001.10:g.215847879del
NC_000001.10:g.215847879delT
NC_000001.10:g.215847880del
NG_009497.1:g.753860del
NM_206933.2:c.13374del
NM_206933.2:c.13374delA
p.Glu4458AspfsX3

Protein change:

E4458fs

Links:

dbSNP: rs727503715

NCBI 1000 Genomes Browser:

rs727503715

Molecular consequence:

NM_206933.4:c.13374del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

Clear Turn Off Turn On

olfactory receptor 1537-like [Mus caroli]
olfactory receptor 1537-like [Mus caroli]
gi|1195666232|ref|XP_021010701.1|

Protein
PREDICTED: Zalophus californianus calpain 3 (CAPN3), transcript variant X5, mRNA
PREDICTED: Zalophus californianus calpain 3 (CAPN3), transcript variant X5, mRNA
gi|1886086557|ref|XM_027572319.2|

Nucleotide
calpain-3 isoform X2 [Zalophus californianus]
calpain-3 isoform X2 [Zalophus californianus]
gi|1543805852|ref|XP_027428117.1|

Protein
histone 3, partial [Acar gradata]
histone 3, partial [Acar gradata]
gi|16118799|gb|AAL14602.1|

Protein
Related BioAssays, by Target Similarity (List) for PubChem BioAss... (751)
Related BioAssays, by Target Similarity (List) for PubChem BioAssay (Select 1913367)
Search

PubChem BioAssay

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
SCV000582685	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Pathogenic (Apr 27, 2017)	germline	clinical testing	Citation Link,
SCV001198901	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Sep 11, 2023)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 10729113, 10909849, 20507924, 25649381, 17405132, 28041643, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000582685

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Pathogenic
(Apr 27, 2017)

germline

clinical testing

Citation Link,

SCV001198901

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Sep 11, 2023)

germline

clinical testing

PubMed (7)
[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	yes	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

Citations

PubMed

Genomic structure and identification of novel mutations in usherin, the gene responsible for Usher syndrome type IIa.

Weston MD, Eudy JD, Fujita S, Yao S, Usami S, Cremers C, Greenberg J, Ramesar R, Martini A, Moller C, Smith RJ, Sumegi J, Kimberling WJ.

Am J Hum Genet. 2000 Apr;66(4):1199-210. Epub 2000 Mar 22. Erratum in: Am J Hum Genet 2000 Jun;66(6):2020. Greenburg J [corrected to Greenberg J].

PubMed [citation]

PMID:: 10729113
PMCID:: PMC1288187

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 (7)

Details of each submission

From GeneDx, SCV000582685.3

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

Description

The c.13374delA variant in the USH2 gene has been reported previously in the compound heterozygous state with a second USH2 variant in patients with Usher syndrome type II (Baux et al., 2007; Le Quesne Stabej et al., 2012). The c.13374delA variant causes a frameshift starting with codon Glutamic Acid 4458, changes this amino acid to a Aspartic Acid residue, and creates a premature Stop codon at position 3 of the new reading frame, denoted p.Glu4458AspfsX3. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.13374delA variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). We interpret c.13374delA as a pathogenic variant.

#	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 Labcorp Genetics (formerly Invitae), Labcorp, SCV001198901.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (7)

Description

This sequence change creates a premature translational stop signal (p.Glu4458Aspfs*3) in the USH2A gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in USH2A are known to be pathogenic (PMID: 10729113, 10909849, 20507924, 25649381). This variant is present in population databases (rs727503715, gnomAD 0.0009%). This premature translational stop signal has been observed in individual(s) with USH2A-related conditions (PMID: 17405132, 28041643). ClinVar contains an entry for this variant (Variation ID: 166428). 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: Nov 10, 2024

ClinVar

Relating variation to medicine