chr12-117520416-C-T

Position:

• chr12-117520416-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.2219+4436G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.766 in 152,104 control chromosomes in the GnomAD database, including 44,780 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 0.77 (44780 hom., cov: 32)
• Consequence: KSR2 NM_173598.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.273

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.936 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KSR2	NM_173598.6	c.2219+4436G>A		intron_variant		ENST00000339824.7	NP_775869.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KSR2	ENST00000339824.7	c.2219+4436G>A		intron_variant		5	NM_173598.6	ENSP00000339952	P1
KSR2	ENST00000545002.1	n.1366-2564G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.766 AC: 116437 AN: 151984 Hom.: 44734 Cov.: 32

Gnomad AFR AF: 0.746

Gnomad AMI AF: 0.708

Gnomad AMR AF: 0.824

Gnomad ASJ AF: 0.745

Gnomad EAS AF: 0.958

Gnomad SAS AF: 0.760

Gnomad FIN AF: 0.728

Gnomad MID AF: 0.718

Gnomad NFE AF: 0.760

Gnomad OTH AF: 0.738

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

GnomAD4 genome AF: 0.766 AC: 116542 AN: 152104 Hom.: 44780 Cov.: 32 AF XY: 0.766 AC XY: 56916 AN XY: 74340

Gnomad4 AFR AF: 0.747

Gnomad4 AMR AF: 0.825

Gnomad4 ASJ AF: 0.745

Gnomad4 EAS AF: 0.958

Gnomad4 SAS AF: 0.762

Gnomad4 FIN AF: 0.728

Gnomad4 NFE AF: 0.760

Gnomad4 OTH AF: 0.735

Alfa AF: 0.761 Hom.: 75994

Bravo AF: 0.775

Asia WGS AF: 0.859 AC: 2985 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.84
DANN	Benign	0.30

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: rs1068932; hg19: chr12-117958221;