rs1309976246
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PP2
The NM_000222.3(KIT):c.2350G>A(p.Ala784Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000558 in 1,612,376 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. A784D) has been classified as Uncertain significance.
Frequency
Consequence
NM_000222.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KIT | NM_000222.3 | c.2350G>A | p.Ala784Thr | missense_variant | 16/21 | ENST00000288135.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KIT | ENST00000288135.6 | c.2350G>A | p.Ala784Thr | missense_variant | 16/21 | 1 | NM_000222.3 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.00000662 AC: 1AN: 151096Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251218Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135786
GnomAD4 exome AF: 0.00000547 AC: 8AN: 1461280Hom.: 0 Cov.: 34 AF XY: 0.00000550 AC XY: 4AN XY: 726938
GnomAD4 genome ? AF: 0.00000662 AC: 1AN: 151096Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 73692
ClinVar
Submissions by phenotype
KIT-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 05, 2024 | The KIT c.2350G>A variant is predicted to result in the amino acid substitution p.Ala784Thr. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0054% of alleles in individuals of East Asian descent in gnomAD and is interpreted as variant of uncertain significance in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/458917/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
Gastrointestinal stromal tumor Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 04, 2023 | This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 784 of the KIT protein (p.Ala784Thr). This variant is present in population databases (no rsID available, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with KIT-related conditions. ClinVar contains an entry for this variant (Variation ID: 458917). 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 disruptive. 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