12-117469701-C-A
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PP3_ModerateBS2
The NM_173598.6(KSR2):c.2807G>T(p.Arg936Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,461,124 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R936H) has been classified as Uncertain significance.
Frequency
Consequence
NM_173598.6 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 rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
KSR2 | NM_173598.6 | c.2807G>T | p.Arg936Leu | missense_variant | Exon 19 of 20 | ENST00000339824.7 | NP_775869.4 | |
KSR2 | XM_011538224.4 | c.2801G>T | p.Arg934Leu | missense_variant | Exon 19 of 20 | XP_011536526.1 | ||
KSR2 | XM_011538225.4 | c.2444G>T | p.Arg815Leu | missense_variant | Exon 19 of 20 | XP_011536527.1 | ||
KSR2 | XM_017019210.3 | c.1502G>T | p.Arg501Leu | missense_variant | Exon 14 of 15 | XP_016874699.1 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.0000121 AC: 3AN: 248178Hom.: 0 AF XY: 0.00000743 AC XY: 1AN XY: 134590
GnomAD4 exome AF: 0.0000130 AC: 19AN: 1461124Hom.: 0 Cov.: 32 AF XY: 0.0000138 AC XY: 10AN XY: 726732
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
KSR2-related disorder Uncertain:1
The KSR2 c.2720G>T variant is predicted to result in the amino acid substitution p.Arg907Leu. This variant was reported in one individual with severe obesity (reported as p.Arg936Leu in Figure 1, Pearce et al. 2013. PubMed ID: 24209692). This variant is reported in 0.0027% of alleles in individuals of European (Non-Finnish) descent in gnomAD. This variant could be pathogenic. However, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at