ClinVar Genomic variation as it relates to human health
NM_206933.4(USH2A):c.675_678del (p.Phe225fs)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_206933.4(USH2A):c.675_678del (p.Phe225fs)
Variation ID: 1074900 Accession: VCV001074900.9
- Type and length
-
Deletion, 4 bp
- Location
-
Cytogenetic: 1q41 1: 216365059-216365062 (GRCh38) [ NCBI UCSC ] 1: 216538401-216538404 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline May 10, 2021 Feb 28, 2024 Nov 4, 2023 - HGVS
-
Nucleotide Protein Molecular
consequenceNM_206933.4:c.675_678del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_996816.3:p.Phe225fs frameshift NM_206933.4:c.675_678delCTTT MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NM_007123.6:c.675_678del NP_009054.6:p.Phe225fs frameshift NC_000001.11:g.216365061_216365064del NC_000001.10:g.216538403_216538406del NG_009497.2:g.63387_63390del - Protein change
- F225fs
- Other names
- -
- Canonical SPDI
- NC_000001.11:216365058:AAAGAA:AA
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
-
-
Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
-
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
-
- Links
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
---|---|---|---|---|---|---|
HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
|||
USH2A | - | - |
GRCh38 GRCh37 |
6937 | 8412 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
---|---|---|---|---|
Pathogenic (1) |
criteria provided, single submitter
|
Jul 6, 2022 | RCV001388346.4 | |
Pathogenic/Likely pathogenic (3) |
criteria provided, multiple submitters, no conflicts
|
Nov 4, 2023 | RCV002307743.5 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
|
---|---|---|---|---|---|
Likely pathogenic
(Feb 25, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Usher syndrome type 2A
Affected status: unknown
Allele origin:
unknown
|
Myriad Genetics, Inc.
Accession: SCV002604301.2
First in ClinVar: Nov 19, 2022 Last updated: Dec 24, 2022 |
Comment:
NM_206933.2(USH2A):c.675_678delCTTT(F225Lfs*17) is expected to be pathogenic in the context of USH2A-related disorders. This variant is predicted to lead to an abnormal or absent protein product … (more)
NM_206933.2(USH2A):c.675_678delCTTT(F225Lfs*17) is expected to be pathogenic in the context of USH2A-related disorders. This variant is predicted to lead to an abnormal or absent protein product due to the creation of a premature termination codon in USH2A, a gene where loss-of-function variants are known to be pathogenic. Please note: this variant was assessed in the context of healthy population screening. (less)
|
|
Pathogenic
(-)
|
criteria provided, single submitter
Method: clinical testing
|
Usher syndrome type 2A
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
|
Lifecell International Pvt. Ltd
Accession: SCV003853260.1
First in ClinVar: Apr 09, 2023 Last updated: Apr 09, 2023 |
Comment:
A Heterozygous Frameshift variant c.675_678delCTTT in Exon 4 of the USH2A gene that results in the premature termination of the protein (p.Phe225fs*17) was identified. The … (more)
A Heterozygous Frameshift variant c.675_678delCTTT in Exon 4 of the USH2A gene that results in the premature termination of the protein (p.Phe225fs*17) was identified. The observed variant has a minimum allele frequency of 0.00% in gnomAD exomes and genomes, respectively. The severity of the impact of this variant on the protein is high, based on the effect of the protein and REVEL score . Rare Exome Variant Ensemble Learner (REVEL) is an ensembl method for predicting the pathogenicity of missense variants based on a combination of scores from 13 individual tools: MutPred, FATHMM v2.3, VEST 3.0, PolyPhen-2, SIFT, PROVEAN, MutationAssessor, MutationTaster, LRT, GERP++, SiPhy, phyloP, and phastCons. The REVEL score for an individual missense variant can range from 0 to 1, with higher scores reflecting greater likelihood that the variant is disease-causing. The variant was found in ClinVar (Variant ID :1074900) with a classification of Pathogenic/Likely Pathogenic and a review status of (2 star) criteria provided, multiple submitters, no conflicts.. Based on the above evidence this variant has been classified as Pathogenic according to the ACMG guidelines. (less)
Ethnicity/Population group: Asian
Geographic origin: India
|
|
Likely pathogenic
(Nov 04, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Usher syndrome type 2A
Affected status: no
Allele origin:
germline
|
Genome-Nilou Lab
Accession: SCV004182960.1
First in ClinVar: Dec 24, 2023 Last updated: Dec 24, 2023 |
|
|
Pathogenic
(Jul 06, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV001589281.4
First in ClinVar: May 10, 2021 Last updated: Feb 28, 2024 |
Comment:
For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 1074900). This variant has not been … (more)
For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 1074900). This variant has not been reported in the literature in individuals affected with USH2A-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Phe225Leufs*17) 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). (less)
|
Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
---|---|---|---|---|
A detailed clinical and molecular survey of subjects with nonsyndromic USH2A retinopathy reveals an allelic hierarchy of disease-causing variants. | Lenassi E | European journal of human genetics : EJHG | 2015 | PMID: 25649381 |
Novel mutations in the long isoform of the USH2A gene in patients with Usher syndrome type II or non-syndromic retinitis pigmentosa. | McGee TL | Journal of medical genetics | 2010 | PMID: 20507924 |
Identification of novel USH2A mutations: implications for the structure of USH2A protein. | Dreyer B | European journal of human genetics : EJHG | 2000 | PMID: 10909849 |
Genomic structure and identification of novel mutations in usherin, the gene responsible for Usher syndrome type IIa. | Weston MD | American journal of human genetics | 2000 | PMID: 10729113 |
Text-mined citations for rs2102708663 ...
HelpRecord last updated Feb 28, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.