NM_206933.4(USH2A):c.14787del (p.Glu4930fs) AND not provided

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Nov 27, 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:: RCV001008087.10

Allele description [Variation Report for NM_206933.4(USH2A):c.14787del (p.Glu4930fs)]

NM_206933.4(USH2A):c.14787del (p.Glu4930fs)

Gene:

USH2A:usherin [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

1q41

Genomic location:

Preferred name:

NM_206933.4(USH2A):c.14787del (p.Glu4930fs)

HGVS:

NC_000001.11:g.215647530del
NG_009497.2:g.780923del
NM_206933.4:c.14787delMANE SELECT
NP_996816.3:p.Glu4930fs
NC_000001.10:g.215820868del
NC_000001.10:g.215820872del
NG_009497.1:g.780871del
NM_206933.2:c.14787del
NM_206933.2:c.14787delA

Protein change:

E4930fs

Links:

dbSNP: rs34713174

NCBI 1000 Genomes Browser:

rs34713174

Molecular consequence:

NM_206933.4:c.14787del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001167831	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Dec 24, 2019)	germline	clinical testing	Citation Link,
SCV001200128	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 27, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 10729113, 10909849, 25649381, 20507924, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001167831

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Dec 24, 2019)

germline

clinical testing

Citation Link,

SCV001200128

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 27, 2023)

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	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 (5)

Details of each submission

From GeneDx, SCV001167831.1

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

Description

Identified in the heterozygous state in an individual with autosomal recessive retinitis pigmentosa, however, it is unknown if this individual harbored a second USH2A variant as limited information was provided in the report (McGee et al., 2010); Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 20507924)

#	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, SCV001200128.5

#	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.Glu4930Asnfs*20) 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 not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with autosomal recessive retinitis pigmentosa (PMID: 20507924). ClinVar contains an entry for this variant (Variation ID: 817032). 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: Sep 29, 2024

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