rs57754754
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1
This summary comes from the ClinGen Evidence Repository: The filtering allele frequency of the c.15297+3A>G variant in the USH2A gene is 0.99% (265/24032) of African chromosomes by the Genome Aggregation Database (http://gnomad.broadinstitute.org; calculated by using inverse allele frequency at https://www.cardiodb.org/allelefrequencyapp/), which is a high enough frequency to be classified as benign based on thresholds defined by the ClinGen Hearing Loss Expert Panel for autosomal recessive hearing loss variants (BA1). LINK:https://erepo.genome.network/evrepo/ui/classification/CA143392/MONDO:0019501/005
Frequency
Consequence
NM_206933.4 splice_donor_region, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
USH2A | NM_206933.4 | c.15297+3A>G | splice_donor_region_variant, intron_variant | ENST00000307340.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
USH2A | ENST00000307340.8 | c.15297+3A>G | splice_donor_region_variant, intron_variant | 1 | NM_206933.4 | P1 | |||
USH2A | ENST00000674083.1 | c.15297+3A>G | splice_donor_region_variant, intron_variant |
Frequencies
GnomAD3 genomes ? AF: 0.00302 AC: 459AN: 152208Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000823 AC: 207AN: 251408Hom.: 1 AF XY: 0.000648 AC XY: 88AN XY: 135878
GnomAD4 exome AF: 0.000331 AC: 484AN: 1461878Hom.: 5 Cov.: 31 AF XY: 0.000267 AC XY: 194AN XY: 727242
GnomAD4 genome ? AF: 0.00301 AC: 459AN: 152326Hom.: 0 Cov.: 32 AF XY: 0.00289 AC XY: 215AN XY: 74496
ClinVar
Submissions by phenotype
not provided Benign:3
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Oct 21, 2019 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 16, 2020 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Apr 25, 2014 | - - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | May 15, 2012 | 15297+3A>G in Intron 70 of USH2A: This variant is not expected to have clinical significance because it has been identified in 1.0% (37/3738) of African America n chromosomes from a broad population by the NHLBI Exome Sequencing Project (htt p://evs.gs.washington.edu/EVS; dbSNP rs57754754). - |
Usher syndrome Benign:1
Benign, reviewed by expert panel | curation | ClinGen Hearing Loss Variant Curation Expert Panel | Sep 14, 2018 | The filtering allele frequency of the c.15297+3A>G variant in the USH2A gene is 0.99% (265/24032) of African chromosomes by the Genome Aggregation Database (http://gnomad.broadinstitute.org; calculated by using inverse allele frequency at https://www.cardiodb.org/allelefrequencyapp/), which is a high enough frequency to be classified as benign based on thresholds defined by the ClinGen Hearing Loss Expert Panel for autosomal recessive hearing loss variants (BA1). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at