NM_206933.4(USH2A):c.3187_3188del (p.Gln1063fs) AND not provided

Germline classification:: Pathogenic (6 submissions)
Last evaluated:: Jun 25, 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:: RCV000254923.19

Allele description [Variation Report for NM_206933.4(USH2A):c.3187_3188del (p.Gln1063fs)]

NM_206933.4(USH2A):c.3187_3188del (p.Gln1063fs)

Genes:

USH2A-AS1:USH2A antisense RNA 1 [Gene - HGNC]
USH2A:usherin [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

1q41

Genomic location:

Preferred name:

NM_206933.4(USH2A):c.3187_3188del (p.Gln1063fs)

Other names:

p.Gln1063Serfs*15

HGVS:

NC_000001.10:g.216380743_216380744del
NC_000001.11:g.216207402_216207403del
NG_009497.2:g.221047_221048del
NM_007123.6:c.3187_3188del
NM_206933.4:c.3187_3188delMANE SELECT
NP_009054.6:p.Gln1063fs
NP_996816.3:p.Gln1063fs
NC_000001.10:g.216380743_216380744del
NC_000001.10:g.216380743_216380744delTG
NC_000001.10:g.216380744_216380745del
NC_000001.10:g.216380744_216380745del
NG_009497.1:g.220995_220996del
NM_206933.2:c.3187_3188del
NM_206933.2:c.3187_3188delCA
NM_206933.3:c.3187_3188delCA
p.Gln1063SerfsX15

Protein change:

Q1063fs

Links:

dbSNP: rs886039450

NCBI 1000 Genomes Browser:

rs886039450

Molecular consequence:

NM_007123.6:c.3187_3188del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_206933.4:c.3187_3188del - frameshift variant - [Sequence Ontology: SO:0001589]

Observations:

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
SCV000321997	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Jun 25, 2024)	germline	clinical testing	Citation Link,
SCV000339777	Eurofins Ntd Llc (ga)	criteria provided, single submitter (EGL Classification Definitions 2015)	Pathogenic (Apr 1, 2016)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 15325563, 18641288, 22135276, 23924366, 25472526 Citation Link,
SCV000957219	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 25, 2023)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 10729113, 10909849, 20507924, 25649381, 23924366, 25472526, 28492532
SCV001448881	Knight Diagnostic Laboratories, Oregon Health and Sciences University	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Dec 19, 2018)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001468005	Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Oct 7, 2020)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004225711	Mayo Clinic Laboratories, Mayo Clinic	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Aug 31, 2022)	germline	clinical testing	PubMed (9) [See all records that cite these PMIDs] 15325563, 18641288, 22135276, 23924366, 25472526, 27624628, 32037395, 34203967, 25741868

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	3	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 (14)

Details of each submission

From GeneDx, SCV000321997.9

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

Description

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 at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 25472526, 15325563, 27624628, 36785559, 34758253, 35266249, 34906470, 32037395, 23924366, 31964843)

#	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 Eurofins Ntd Llc (ga), SCV000339777.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (5)

#	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		1	not provided	not provided	not provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000957219.6

#	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.Gln1063Serfs*15) 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 (no rsID available, gnomAD 0.01%). This premature translational stop signal has been observed in individual(s) with retinitis pigemntosa and/or Usher syndrome type 2 (PMID: 23924366, 25472526). ClinVar contains an entry for this variant (Variation ID: 265288). 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

From Knight Diagnostic Laboratories, Oregon Health and Sciences University, SCV001448881.1

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

From Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center, SCV001468005.1

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

Description

PVS1, PS4

#	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 Mayo Clinic Laboratories, Mayo Clinic, SCV004225711.1

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

Description

PM2, PM3_strong, PVS1

#	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		1	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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