rs114116572
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 4P and 5B. PM1PM2BP4_StrongBP6
The NM_206933.4(USH2A):āc.12598T>Gā(p.Trp4200Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000123 in 1,614,084 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_206933.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
USH2A | NM_206933.4 | c.12598T>G | p.Trp4200Gly | missense_variant | 63/72 | ENST00000307340.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
USH2A | ENST00000307340.8 | c.12598T>G | p.Trp4200Gly | missense_variant | 63/72 | 1 | NM_206933.4 | P1 | |
USH2A | ENST00000674083.1 | c.12598T>G | p.Trp4200Gly | missense_variant | 63/73 |
Frequencies
GnomAD3 genomes ? AF: 0.000611 AC: 93AN: 152176Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000217 AC: 54AN: 249236Hom.: 0 AF XY: 0.000156 AC XY: 21AN XY: 134884
GnomAD4 exome AF: 0.0000718 AC: 105AN: 1461790Hom.: 0 Cov.: 37 AF XY: 0.0000550 AC XY: 40AN XY: 727188
GnomAD4 genome ? AF: 0.000611 AC: 93AN: 152294Hom.: 0 Cov.: 32 AF XY: 0.000524 AC XY: 39AN XY: 74476
ClinVar
Submissions by phenotype
not provided Uncertain:2Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Apr 14, 2016 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 06, 2024 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jun 16, 2021 | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 27535533) - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 06, 2021 | The c.12598T>G (p.W4200G) alteration is located in exon 63 (coding exon 62) of the USH2A gene. This alteration results from a T to G substitution at nucleotide position 12598, causing the tryptophan (W) at amino acid position 4200 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Usher syndrome type 2A Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Nov 06, 2019 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jun 03, 2014 | Trp4200Gly in exon 63 of USH2A: This variant is not expected to have clinical si gnificance due to a lack of conservation across species, including mammals. Of n ote, at least 5 mammals (dolphin, killer whale, hedgehog, star-nosed mole, and c ape-golden mole) have a glycine (Gly) at this position despite high nearby amino acid conservation. In addition, it was identified in 0.6% (1/176) of African ch romosomes by the 1000 Genomes Project (http://www.1000genomes.org; dbSNP rs11411 6572). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at