rs727503727
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The NM_206933.4(USH2A):c.5858-12A>G variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,613,538 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_206933.4 splice_polypyrimidine_tract, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
USH2A | NM_206933.4 | c.5858-12A>G | splice_polypyrimidine_tract_variant, intron_variant | ENST00000307340.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
USH2A | ENST00000307340.8 | c.5858-12A>G | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_206933.4 | P1 | |||
USH2A | ENST00000674083.1 | c.5858-12A>G | splice_polypyrimidine_tract_variant, intron_variant |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152158Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000797 AC: 2AN: 250874Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135600
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461380Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 726996
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152158Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74316
ClinVar
Submissions by phenotype
Usher syndrome type 2A;C3151138:Retinitis pigmentosa 39 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Counsyl | Sep 26, 2017 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Dec 12, 2013 | 5858-12A>G in Intron 29 of USH2A: This variant is not expected to have clinical significance because it is not located in the invariant -1/-2 positions of the s plice site consensus sequence and computational tools do not predict an impact t o splicing. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 17, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at