12-117544415-C-T

Position:

• chr12-117544415-C-T

Variant summary

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

The NM_173598.6(KSR2):​c.1519-4528G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.346 in 151,814 control chromosomes in the GnomAD database, including 9,422 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 0.35 (9422 hom., cov: 31)
• Consequence: KSR2 NM_173598.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.196

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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.401 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KSR2	NM_173598.6	c.1519-4528G>A		intron_variant		ENST00000339824.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KSR2	ENST00000339824.7	c.1519-4528G>A		intron_variant		5	NM_173598.6	P1
KSR2	ENST00000543793.1	n.62-4528G>A		intron_variant, non_coding_transcript_variant		3
KSR2	ENST00000545002.1	n.665-4528G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.346 AC: 52515 AN: 151698 Hom.: 9426 Cov.: 31

Gnomad AFR AF: 0.280

Gnomad AMI AF: 0.261

Gnomad AMR AF: 0.294

Gnomad ASJ AF: 0.340

Gnomad EAS AF: 0.173

Gnomad SAS AF: 0.361

Gnomad FIN AF: 0.394

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.405

Gnomad OTH AF: 0.330

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

GnomAD4 genome AF: 0.346 AC: 52519 AN: 151814 Hom.: 9422 Cov.: 31 AF XY: 0.341 AC XY: 25300 AN XY: 74200

Gnomad4 AFR AF: 0.280

Gnomad4 AMR AF: 0.293

Gnomad4 ASJ AF: 0.340

Gnomad4 EAS AF: 0.173

Gnomad4 SAS AF: 0.362

Gnomad4 FIN AF: 0.394

Gnomad4 NFE AF: 0.405

Gnomad4 OTH AF: 0.329

Alfa AF: 0.370 Hom.: 1326

Bravo AF: 0.335

Asia WGS AF: 0.262 AC: 915 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.94
DANN	Benign	0.90

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: rs7964157; hg19: chr12-117982220;