9-128633797-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_052844.4(DYNC2I2):c.1558G>A(p.Gly520Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,268 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_052844.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DYNC2I2 | ENST00000372715.7 | c.1558G>A | p.Gly520Arg | missense_variant | Exon 9 of 9 | 1 | NM_052844.4 | ENSP00000361800.2 | ||
SPTAN1 | ENST00000372739.7 | c.*463C>T | downstream_gene_variant | 1 | NM_001130438.3 | ENSP00000361824.4 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251070Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135848
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461268Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4AN XY: 726958
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Short-rib thoracic dysplasia 11 with or without polydactyly Uncertain:1
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. This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 520 of the WDR34 protein (p.Gly520Arg). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with WDR34-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at