rs6660707
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_206933.4(USH2A):c.9723C>T(p.Tyr3241=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00119 in 1,613,840 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0064 ( 8 hom., cov: 32)
Exomes 𝑓: 0.00065 ( 9 hom. )
Consequence
USH2A
NM_206933.4 synonymous
NM_206933.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.734
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 -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.79).
BP6
?
Variant 1-215813752-G-A is Benign according to our data. Variant chr1-215813752-G-A is described in ClinVar as [Benign]. Clinvar id is 48633.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-215813752-G-A is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=-0.734 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00637 (970/152224) while in subpopulation AFR AF= 0.0221 (919/41534). AF 95% confidence interval is 0.0209. There are 8 homozygotes in gnomad4. There are 437 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 8 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
USH2A | NM_206933.4 | c.9723C>T | p.Tyr3241= | synonymous_variant | 49/72 | ENST00000307340.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
USH2A | ENST00000307340.8 | c.9723C>T | p.Tyr3241= | synonymous_variant | 49/72 | 1 | NM_206933.4 | P1 | |
USH2A | ENST00000674083.1 | c.9723C>T | p.Tyr3241= | synonymous_variant | 49/73 |
Frequencies
GnomAD3 genomes ? AF: 0.00634 AC: 965AN: 152106Hom.: 8 Cov.: 32
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GnomAD3 exomes AF: 0.00151 AC: 379AN: 251244Hom.: 2 AF XY: 0.00107 AC XY: 145AN XY: 135758
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GnomAD4 exome AF: 0.000652 AC: 953AN: 1461616Hom.: 9 Cov.: 31 AF XY: 0.000543 AC XY: 395AN XY: 727104
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ClinVar
Significance: Benign
Submissions summary: Benign:8
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:3
Benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Apr 27, 2012 | Tyr3241Tyr in exon 49 of USH2A: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue, is not located withi n the splice consensus sequence, has been identified in 2% (73/3738) of African American chromosomes from a broad population by the NHLBI Exome sequencing proje ct (http://evs.gs.washington.edu/EVS/; dbSNP rs6660707). - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Usher syndrome type 2A Benign:2
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Nov 04, 2023 | - - |
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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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at