chr12-117567836-C-A

Position:

• chr12-117567836-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_173598.6(KSR2):​c.1326-9263G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.463 in 144,730 control chromosomes in the GnomAD database, including 15,835 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.46 (15835 hom., cov: 28)
• Consequence: KSR2 NM_173598.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.31

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.527 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KSR2	NM_173598.6	c.1326-9263G>T		intron_variant		ENST00000339824.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KSR2	ENST00000339824.7	c.1326-9263G>T		intron_variant		5	NM_173598.6	P1
KSR2	ENST00000545002.1	n.472-9263G>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.463 AC: 66924 AN: 144618 Hom.: 15835 Cov.: 28

Gnomad AFR AF: 0.338

Gnomad AMI AF: 0.555

Gnomad AMR AF: 0.471

Gnomad ASJ AF: 0.539

Gnomad EAS AF: 0.470

Gnomad SAS AF: 0.546

Gnomad FIN AF: 0.568

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.500

Gnomad OTH AF: 0.471

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.463 AC: 66952 AN: 144730 Hom.: 15835 Cov.: 28 AF XY: 0.466 AC XY: 32946 AN XY: 70660

Gnomad4 AFR AF: 0.338

Gnomad4 AMR AF: 0.472

Gnomad4 ASJ AF: 0.539

Gnomad4 EAS AF: 0.470

Gnomad4 SAS AF: 0.545

Gnomad4 FIN AF: 0.568

Gnomad4 NFE AF: 0.500

Gnomad4 OTH AF: 0.467

Alfa AF: 0.484 Hom.: 10172

Bravo AF: 0.442

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.42
DANN	Benign	0.55

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs11068544; hg19: chr12-118005641;