chr1-215625812-TC-T
Variant names:
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PVS1_ModeratePM2
The NM_206933.4(USH2A):c.15577delG(p.Glu5193AsnfsTer40) variant causes a frameshift change. The variant allele was found at a frequency of 0.00000137 in 1,461,816 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
USH2A
NM_206933.4 frameshift
NM_206933.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 5.39
Genes affected
USH2A (HGNC:12601): (usherin) This gene encodes a protein that contains laminin EGF motifs, a pentaxin domain, and many fibronectin type III motifs. The protein is found in the basement membrane, and may be important in development and homeostasis of the inner ear and retina. Mutations within this gene have been associated with Usher syndrome type IIa and retinitis pigmentosa. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.00205 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| USH2A | ENST00000307340.8 | c.15577delG | p.Glu5193AsnfsTer40 | frameshift_variant | Exon 72 of 72 | 1 | NM_206933.4 | ENSP00000305941.3 | ||
| USH2A | ENST00000674083.1 | c.15649delG | p.Glu5217AsnfsTer40 | frameshift_variant | Exon 73 of 73 | ENSP00000501296.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461816Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 727208
GnomAD4 exome
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1461816
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30
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0
AN XY:
727208
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GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Usher syndrome type 2A;C3151138:Retinitis pigmentosa 39 Uncertain:3
Sep 05, 2017
Counsyl
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
Oct 06, 2021
Fulgent Genetics, Fulgent Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
Jul 06, 2023
Intergen, Intergen Genetics and Rare Diseases Diagnosis Center
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
Retinitis pigmentosa 39 Uncertain:1
Nov 04, 2023
Genome-Nilou Lab
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
Usher syndrome type 2A Uncertain:1
Nov 04, 2023
Genome-Nilou Lab
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
Computational scores
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at