12-117469701-C-T
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BS2
The NM_173598.6(KSR2):c.2807G>A(p.Arg936His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000118 in 1,613,384 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).
Frequency
Consequence
NM_173598.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
KSR2 | NM_173598.6 | c.2807G>A | p.Arg936His | missense_variant | Exon 19 of 20 | ENST00000339824.7 | NP_775869.4 | |
KSR2 | XM_011538224.4 | c.2801G>A | p.Arg934His | missense_variant | Exon 19 of 20 | XP_011536526.1 | ||
KSR2 | XM_011538225.4 | c.2444G>A | p.Arg815His | missense_variant | Exon 19 of 20 | XP_011536527.1 | ||
KSR2 | XM_017019210.3 | c.1502G>A | p.Arg501His | missense_variant | Exon 14 of 15 | XP_016874699.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152142Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000403 AC: 1AN: 248178Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 134590
GnomAD4 exome AF: 0.0000123 AC: 18AN: 1461124Hom.: 0 Cov.: 32 AF XY: 0.00000963 AC XY: 7AN XY: 726732
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152260Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74454
ClinVar
Submissions by phenotype
KSR2-related disorder Uncertain:1
The KSR2 c.2720G>A variant is predicted to result in the amino acid substitution p.Arg907His. This variant has been reported as a somatic variant in an individual with atypical Von Hippel‑Lindau syndrome (Tong et al. 2021. PubMed ID: 34923986). This variant is reported in 0.010% of alleles in individuals of Ashkenazi Jewish descent in gnomAD. 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