rs201401001
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6BP7
The NM_206933.4(USH2A):c.10470G>T(p.Val3490=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000595 in 1,613,932 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.00037 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00062 ( 2 hom. )
Consequence
USH2A
NM_206933.4 synonymous
NM_206933.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.606
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 Likely_benign. Variant got -6 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.56).
BP6
?
Variant 1-215782853-C-A is Benign according to our data. Variant chr1-215782853-C-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 48346.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=4, Uncertain_significance=1}.
BP7
?
Synonymous conserved (PhyloP=0.606 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
USH2A | NM_206933.4 | c.10470G>T | p.Val3490= | synonymous_variant | 53/72 | ENST00000307340.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
USH2A | ENST00000307340.8 | c.10470G>T | p.Val3490= | synonymous_variant | 53/72 | 1 | NM_206933.4 | P1 | |
USH2A | ENST00000674083.1 | c.10470G>T | p.Val3490= | synonymous_variant | 53/73 |
Frequencies
GnomAD3 genomes ? AF: 0.000375 AC: 57AN: 152148Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000247 AC: 62AN: 251062Hom.: 0 AF XY: 0.000265 AC XY: 36AN XY: 135662
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GnomAD4 exome AF: 0.000619 AC: 905AN: 1461666Hom.: 2 Cov.: 31 AF XY: 0.000582 AC XY: 423AN XY: 727120
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GnomAD4 genome ? AF: 0.000368 AC: 56AN: 152266Hom.: 0 Cov.: 33 AF XY: 0.000430 AC XY: 32AN XY: 74462
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:4
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Uncertain:1Benign:3
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | May 04, 2018 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Nov 16, 2017 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 30, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Apr 01, 2023 | USH2A: BP4, BP7 - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Apr 30, 2012 | Val3490Val in Exon 53 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, and has been identified in 1/7020 European Amer ican chromosomes from a broad population by the NHLBI Exome Sequencing Project ( http://evs.gs.washington.edu/EVS). - |
Computational scores
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BayesDel_noAF
Benign
Cadd
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Dann
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at