chr12-117469751-A-G
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_173598.6(KSR2):c.2757T>C(p.Pro919=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00135 in 1,613,944 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0069 ( 16 hom., cov: 32)
Exomes 𝑓: 0.00077 ( 13 hom. )
Consequence
KSR2
NM_173598.6 synonymous
NM_173598.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0200
Genes affected
KSR2 (HGNC:18610): (kinase suppressor of ras 2) Predicted to enable MAP-kinase scaffold activity; mitogen-activated protein kinase kinase binding activity; and protein kinase activity. Predicted to be involved in Ras protein signal transduction; calcium-mediated signaling; and positive regulation of cold-induced thermogenesis. Predicted to act upstream of or within positive regulation of MAPK cascade. Predicted to be active in cytosol and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.53).
BP6
?
Variant 12-117469751-A-G is Benign according to our data. Variant chr12-117469751-A-G is described in ClinVar as [Benign]. Clinvar id is 768590.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-0.02 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00688 (1048/152344) while in subpopulation AFR AF= 0.0234 (974/41568). AF 95% confidence interval is 0.0222. There are 16 homozygotes in gnomad4. There are 488 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd at 1034 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KSR2 | NM_173598.6 | c.2757T>C | p.Pro919= | synonymous_variant | 19/20 | ENST00000339824.7 | |
KSR2 | XM_011538224.4 | c.2751T>C | p.Pro917= | synonymous_variant | 19/20 | ||
KSR2 | XM_011538225.4 | c.2394T>C | p.Pro798= | synonymous_variant | 19/20 | ||
KSR2 | XM_017019210.3 | c.1452T>C | p.Pro484= | synonymous_variant | 14/15 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KSR2 | ENST00000339824.7 | c.2757T>C | p.Pro919= | synonymous_variant | 19/20 | 5 | NM_173598.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00679 AC: 1034AN: 152226Hom.: 15 Cov.: 32
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GnomAD3 exomes AF: 0.00171 AC: 427AN: 249044Hom.: 4 AF XY: 0.00137 AC XY: 185AN XY: 135086
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GnomAD4 exome AF: 0.000771 AC: 1127AN: 1461600Hom.: 13 Cov.: 32 AF XY: 0.000682 AC XY: 496AN XY: 727062
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Jul 21, 2021 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 22, 2024 | - - |
KSR2-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Apr 29, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at