rs201558076
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 0P and 3B. BP4_ModerateBP6
The ENST00000307340.8(USH2A):c.3158-7A>G variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000159 in 1,613,844 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
ENST00000307340.8 splice_region, splice_polypyrimidine_tract, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
USH2A | NM_206933.4 | c.3158-7A>G | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000307340.8 | NP_996816.3 | |||
USH2A-AS1 | XR_922596.4 | n.691+11513T>C | intron_variant, non_coding_transcript_variant | |||||
USH2A | NM_007123.6 | c.3158-7A>G | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | NP_009054.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
USH2A | ENST00000307340.8 | c.3158-7A>G | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_206933.4 | ENSP00000305941 | P1 | |||
USH2A | ENST00000366942.3 | c.3158-7A>G | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | ENSP00000355909 | |||||
USH2A | ENST00000674083.1 | c.3158-7A>G | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENSP00000501296 |
Frequencies
GnomAD3 genomes AF: 0.000881 AC: 134AN: 152092Hom.: 1 Cov.: 32
GnomAD3 exomes AF: 0.000191 AC: 48AN: 250944Hom.: 0 AF XY: 0.000118 AC XY: 16AN XY: 135622
GnomAD4 exome AF: 0.0000814 AC: 119AN: 1461634Hom.: 1 Cov.: 31 AF XY: 0.0000646 AC XY: 47AN XY: 727106
GnomAD4 genome AF: 0.000900 AC: 137AN: 152210Hom.: 1 Cov.: 32 AF XY: 0.000995 AC XY: 74AN XY: 74408
ClinVar
Submissions by phenotype
not specified Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Feb 26, 2015 | c.3158-7A>G in intron 15 of USH2A: This variant is not expected to have clinical significance because it has been identified in 0.3% (28/10558) of African chrom osomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.or g; dbSNP rs201558076). - |
Uncertain significance, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | May 15, 2024 | Variant summary: USH2A c.3158-7A>G alters a conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. Consensus agreement among computation tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00016 in 1613844 control chromosomes, predominantly at a frequency of 0.0029 within the African or African-American subpopulation in the gnomAD database, including 2 homozygotes. This frequency is not significantly higher than estimated for a pathogenic variant in USH2A causing Usher Syndrome (0.00016 vs 0.011), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.3158-7A>G in individuals affected with Usher Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 228212). Based on the evidence outlined above, the variant was classified as VUS-possibly benign. - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 28, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 31, 2020 | - - |
Retinitis pigmentosa 39 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Apr 11, 2023 | - - |
Usher syndrome type 2A Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Apr 11, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at