rs397518004
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1PM2BP4_Moderate
The NM_206933.4(USH2A):c.1934C>T(p.Thr645Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. T645T) has been classified as Likely benign.
Frequency
Consequence
NM_206933.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
USH2A | NM_206933.4 | c.1934C>T | p.Thr645Ile | missense_variant | 11/72 | ENST00000307340.8 | |
USH2A | NM_007123.6 | c.1934C>T | p.Thr645Ile | missense_variant | 11/21 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
USH2A | ENST00000307340.8 | c.1934C>T | p.Thr645Ile | missense_variant | 11/72 | 1 | NM_206933.4 | P1 | |
USH2A | ENST00000366942.3 | c.1934C>T | p.Thr645Ile | missense_variant | 11/21 | 1 | |||
USH2A | ENST00000674083.1 | c.1934C>T | p.Thr645Ile | missense_variant | 11/73 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome Cov.: 31
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Aug 14, 2013 | Variant classified as Uncertain Significance - Favor Benign. The Thr645Ile varia nt in USH2A has not been reported in affected individuals or in large population studies. This amino acid is not conserved in mammals, including primates, and c omputational analyses (biochemical amino acid properties, conservation, AlignGVG D, PolyPhen2, and SIFT) suggest that the Thr645Ile variant may not impact the pr otein, though this information is not predictive enough to rule out pathogenicit y. In summary, additional information is needed to determine the clinical signif icance of this variant; however, we would lean towards a more likely benign role . - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at