rs10444502

Positions:

• chr12-117916066-A-C
• chr12-117916066-A-G
• chr12-117916066-A-T

Variant summary

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

The NM_173598.6(KSR2):​c.180+52010T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.405 in 150,918 control chromosomes in the GnomAD database, including 13,386 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 0.41 (13386 hom., cov: 29)
• Consequence: KSR2 NM_173598.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.563

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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.683 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KSR2	NM_173598.6	c.180+52010T>G		intron_variant		ENST00000339824.7	NP_775869.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KSR2	ENST00000339824.7	c.180+52010T>G		intron_variant		5	NM_173598.6	ENSP00000339952	P1

Frequencies

GnomAD3 genomes AF: 0.405 AC: 61107 AN: 150804 Hom.: 13342 Cov.: 29

Gnomad AFR AF: 0.514

Gnomad AMI AF: 0.449

Gnomad AMR AF: 0.462

Gnomad ASJ AF: 0.394

Gnomad EAS AF: 0.702

Gnomad SAS AF: 0.501

Gnomad FIN AF: 0.311

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.314

Gnomad OTH AF: 0.376

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

GnomAD4 genome AF: 0.405 AC: 61196 AN: 150918 Hom.: 13386 Cov.: 29 AF XY: 0.410 AC XY: 30174 AN XY: 73610

Gnomad4 AFR AF: 0.514

Gnomad4 AMR AF: 0.462

Gnomad4 ASJ AF: 0.394

Gnomad4 EAS AF: 0.702

Gnomad4 SAS AF: 0.500

Gnomad4 FIN AF: 0.311

Gnomad4 NFE AF: 0.314

Gnomad4 OTH AF: 0.384

Alfa AF: 0.340 Hom.: 20268

Bravo AF: 0.424

Asia WGS AF: 0.636 AC: 2211 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.2
DANN	Benign	0.57

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: rs10444502; hg19: chr12-118353871;