rs1215540106
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PM4_SupportingPP5
The NM_206933.4(USH2A):c.3831_3834delinsG(p.Leu1278del) variant causes a protein altering change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (no stars). Synonymous variant affecting the same amino acid position (i.e. E1277E) has been classified as Likely benign.
Frequency
Genomes: not found (cov: 32)
Consequence
USH2A
NM_206933.4 protein_altering
NM_206933.4 protein_altering
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 5.93
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.
PM2
?
Very rare variant in population databases, with high coverage;
PM4
?
Nonframeshift variant in NON repetitive region in NM_206933.4. Strenght limited to Supporting due to length of the change: 1aa.
PP5
?
Variant 1-216198562-TAGT-C is Pathogenic according to our data. Variant chr1-216198562-TAGT-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 438019.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
USH2A | NM_206933.4 | c.3831_3834delinsG | p.Leu1278del | protein_altering_variant | 18/72 | ENST00000307340.8 | |
USH2A-AS1 | XR_922596.4 | n.691+2637_691+2640delinsC | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
USH2A | ENST00000307340.8 | c.3831_3834delinsG | p.Leu1278del | protein_altering_variant | 18/72 | 1 | NM_206933.4 | P1 | |
USH2A | ENST00000366942.3 | c.3831_3834delinsG | p.Leu1278del | protein_altering_variant | 18/21 | 1 | |||
USH2A-AS1 | ENST00000420867.1 | n.362+2637_362+2640delinsC | intron_variant, non_coding_transcript_variant | 3 | |||||
USH2A | ENST00000674083.1 | c.3831_3834delinsG | p.Leu1278del | protein_altering_variant | 18/73 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Usher syndrome Pathogenic:1
Likely pathogenic, no assertion criteria provided | research | NIHR Bioresource Rare Diseases, University of Cambridge | Jan 01, 2015 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at