rs727503734
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM1PM2BP4
The NM_206933.4(USH2A):c.3493G>C(p.Val1165Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000496 in 1,613,984 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 Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. V1165V) has been classified as Likely benign.
Frequency
Consequence
NM_206933.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
USH2A | NM_206933.4 | c.3493G>C | p.Val1165Leu | missense_variant | 17/72 | ENST00000307340.8 | |
USH2A-AS1 | XR_922596.4 | n.691+4020C>G | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
USH2A | ENST00000307340.8 | c.3493G>C | p.Val1165Leu | missense_variant | 17/72 | 1 | NM_206933.4 | P1 | |
USH2A | ENST00000366942.3 | c.3493G>C | p.Val1165Leu | missense_variant | 17/21 | 1 | |||
USH2A-AS1 | ENST00000420867.1 | n.362+4020C>G | intron_variant, non_coding_transcript_variant | 3 | |||||
USH2A | ENST00000674083.1 | c.3493G>C | p.Val1165Leu | missense_variant | 17/73 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152154Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251180Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135744
GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461830Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4AN XY: 727220
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152154Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74330
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 | Oct 05, 2013 | Variant classified as Uncertain Significance - Favor Benign. The Val1165Leu vari ant in USH2A has not been reported in individuals with hearing loss or in large population studies. Computational analyses (biochemical amino acid properties, conservation, AlignGVGD, PolyPhen2, and SIFT) suggest that the Val1165Leu varian t may not impact the protein, though this information is not predictive enough t o rule out pathogenicity. In summary, the clinical significance of this variant cannot be determined with certainty; however based upon conservation and computa tional data, we would lean towards a more likely benign role. - |
Usher syndrome type 2A;C3151138:Retinitis pigmentosa 39 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Counsyl | Nov 21, 2017 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Oct 01, 2016 | - - |
Retinitis pigmentosa 39 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Nov 04, 2023 | - - |
Usher syndrome type 2A Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Nov 04, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at