rs727503730
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 6P and 2B. PM1PM2PM5BP4_Moderate
The NM_206933.4(USH2A):c.4559T>A(p.Ile1520Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,613,696 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I1520F) has been classified as Uncertain significance.
Frequency
Consequence
NM_206933.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
USH2A | NM_206933.4 | c.4559T>A | p.Ile1520Asn | missense_variant | 21/72 | ENST00000307340.8 | |
USH2A | NM_007123.6 | c.4559T>A | p.Ile1520Asn | missense_variant | 21/21 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
USH2A | ENST00000307340.8 | c.4559T>A | p.Ile1520Asn | missense_variant | 21/72 | 1 | NM_206933.4 | P1 | |
USH2A | ENST00000366942.3 | c.4559T>A | p.Ile1520Asn | missense_variant | 21/21 | 1 | |||
USH2A | ENST00000674083.1 | c.4559T>A | p.Ile1520Asn | missense_variant | 21/73 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152170Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461526Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727056
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152170Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74328
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 | Nov 22, 2013 | The Ile1520Asn variant in USH2A has not been previously reported in individuals with hearing loss or in large population studies. Computational analyses (amino acid biochemical properties, conservation, AlignGVGD, PolyPhen2, SIFT) do not p rovide strong evidence for or against an impact to the protein. In summary, add itional data is needed to fully assess the clinical significance of this variant . - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at