2-8730839-T-C
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 3P and 5B. PM2PP2BP4_StrongBP6
The NM_020738.4(KIDINS220):c.5197A>G(p.Thr1733Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000291 in 1,614,120 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_020738.4 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 |
---|---|---|---|---|---|---|---|
KIDINS220 | NM_020738.4 | c.5197A>G | p.Thr1733Ala | missense_variant | 30/30 | ENST00000256707.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KIDINS220 | ENST00000256707.8 | c.5197A>G | p.Thr1733Ala | missense_variant | 30/30 | 1 | NM_020738.4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152230Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000160 AC: 4AN: 249578Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135406
GnomAD4 exome AF: 0.0000301 AC: 44AN: 1461890Hom.: 0 Cov.: 37 AF XY: 0.0000303 AC XY: 22AN XY: 727248
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152230Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74380
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 31, 2022 | Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The alanine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. This variant has not been reported in the literature in individuals affected with KIDINS220-related conditions. This variant is present in population databases (rs769837969, gnomAD 0.003%). This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 1733 of the KIDINS220 protein (p.Thr1733Ala). 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. - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 24, 2022 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at