chr12-117484478-G-A
Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_173598.6(KSR2):c.2388C>T(p.Asn796=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000948 in 1,613,910 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000099 ( 0 hom. )
Consequence
KSR2
NM_173598.6 synonymous
NM_173598.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.06
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 -17 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BP6
?
Variant 12-117484478-G-A is Benign according to our data. Variant chr12-117484478-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2082781.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-2.06 with no splicing effect.
BS2
?
High AC in GnomAd at 8 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KSR2 | NM_173598.6 | c.2388C>T | p.Asn796= | synonymous_variant | 16/20 | ENST00000339824.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KSR2 | ENST00000339824.7 | c.2388C>T | p.Asn796= | synonymous_variant | 16/20 | 5 | NM_173598.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000525 AC: 8AN: 152254Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000116 AC: 29AN: 249036Hom.: 0 AF XY: 0.000104 AC XY: 14AN XY: 135110
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GnomAD4 exome AF: 0.0000992 AC: 145AN: 1461538Hom.: 0 Cov.: 31 AF XY: 0.0000867 AC XY: 63AN XY: 727044
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GnomAD4 genome ? AF: 0.0000525 AC: 8AN: 152372Hom.: 0 Cov.: 32 AF XY: 0.0000537 AC XY: 4AN XY: 74504
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jul 03, 2022 | - - |
KSR2-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 17, 2020 | This variant is classified as likely 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
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at