rs73090721
Positions:
Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_206933.4(USH2A):c.9459C>T(p.Cys3153=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00072 in 1,612,782 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0039 ( 4 hom., cov: 32)
Exomes 𝑓: 0.00039 ( 5 hom. )
Consequence
USH2A
NM_206933.4 synonymous
NM_206933.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.919
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 Benign. Variant got -17 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.56).
BP6
?
Variant 1-215817108-G-A is Benign according to our data. Variant chr1-215817108-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 178645.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-215817108-G-A is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=0.919 with no splicing effect.
BS2
?
High Homozygotes in GnomAd4 at 4 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
USH2A | NM_206933.4 | c.9459C>T | p.Cys3153= | synonymous_variant | 48/72 | ENST00000307340.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
USH2A | ENST00000307340.8 | c.9459C>T | p.Cys3153= | synonymous_variant | 48/72 | 1 | NM_206933.4 | P1 | |
USH2A | ENST00000674083.1 | c.9459C>T | p.Cys3153= | synonymous_variant | 48/73 |
Frequencies
GnomAD3 genomes ? AF: 0.00392 AC: 595AN: 151868Hom.: 4 Cov.: 32
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GnomAD3 exomes AF: 0.00113 AC: 283AN: 250418Hom.: 4 AF XY: 0.000783 AC XY: 106AN XY: 135308
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GnomAD4 exome AF: 0.000387 AC: 565AN: 1460794Hom.: 5 Cov.: 30 AF XY: 0.000341 AC XY: 248AN XY: 726696
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GnomAD4 genome ? AF: 0.00393 AC: 597AN: 151988Hom.: 4 Cov.: 32 AF XY: 0.00386 AC XY: 287AN XY: 74286
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:8
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:3
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Dec 01, 2022 | USH2A: BP4, BP7 - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 03, 2019 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Usher syndrome type 2A Benign:2
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Dec 10, 2019 | - - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Nov 04, 2023 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | May 07, 2012 | Cys3153Cys in Exon 48 of USH2A: This variant is not expected to have clinical s ignificance because it does not alter an amino acid residue, is not located with in the splice consensus sequence, and has been identified in 1.6% (59/3738) of A frican American chromosomes from a broad population by the NHLBI Exome Sequencin g Project (http://evs.gs.washington.edu/EVS; dbSNP rs73090721). - |
Usher syndrome type 2A;C3151138:Retinitis pigmentosa 39 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | May 20, 2022 | - - |
Retinitis pigmentosa 39 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Nov 04, 2023 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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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