rs370850399
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_018051.5(DYNC2I1):c.3077C>T(p.Ala1026Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000062 in 1,612,256 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. A1026A) has been classified as Likely benign.
Frequency
Consequence
NM_018051.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DYNC2I1 | NM_018051.5 | c.3077C>T | p.Ala1026Val | missense_variant | 25/25 | ENST00000407559.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DYNC2I1 | ENST00000407559.8 | c.3077C>T | p.Ala1026Val | missense_variant | 25/25 | 1 | NM_018051.5 | P1 | |
DYNC2I1 | ENST00000444851.5 | c.*666C>T | 3_prime_UTR_variant, NMD_transcript_variant | 20/20 | 1 | ||||
DYNC2I1 | ENST00000467220.1 | n.4876C>T | non_coding_transcript_exon_variant | 20/20 | 2 | ||||
DYNC2I1 | ENST00000454771.1 | c.467C>T | p.Ala156Val | missense_variant, NMD_transcript_variant | 4/5 | 4 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152184Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000821 AC: 2AN: 243716Hom.: 0 AF XY: 0.0000151 AC XY: 2AN XY: 132668
GnomAD4 exome AF: 0.00000548 AC: 8AN: 1460072Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 726188
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152184Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74344
ClinVar
Submissions by phenotype
Short-rib thoracic dysplasia 8 with or without polydactyly Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 15, 2023 | This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1026 of the WDR60 protein (p.Ala1026Val). This variant is present in population databases (rs370850399, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with WDR60-related conditions. ClinVar contains an entry for this variant (Variation ID: 474629). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at