12-117741905-T-C

Position:

• chr12-117741905-T-C

Variant summary

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

The NM_173598.6(KSR2):​c.986+19106A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.902 in 152,232 control chromosomes in the GnomAD database, including 62,186 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 0.90 (62186 hom., cov: 31)
• Consequence: KSR2 NM_173598.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.528

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 = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KSR2	NM_173598.6	c.986+19106A>G		intron_variant		ENST00000339824.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KSR2	ENST00000339824.7	c.986+19106A>G		intron_variant		5	NM_173598.6	P1

Frequencies

GnomAD3 genomes AF: 0.901 AC: 137118 AN: 152114 Hom.: 62124 Cov.: 31

Gnomad AFR AF: 0.976

Gnomad AMI AF: 0.935

Gnomad AMR AF: 0.923

Gnomad ASJ AF: 0.934

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.942

Gnomad FIN AF: 0.765

Gnomad MID AF: 0.940

Gnomad NFE AF: 0.859

Gnomad OTH AF: 0.922

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

GnomAD4 genome AF: 0.902 AC: 137239 AN: 152232 Hom.: 62186 Cov.: 31 AF XY: 0.901 AC XY: 67017 AN XY: 74406

Gnomad4 AFR AF: 0.976

Gnomad4 AMR AF: 0.923

Gnomad4 ASJ AF: 0.934

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.942

Gnomad4 FIN AF: 0.765

Gnomad4 NFE AF: 0.859

Gnomad4 OTH AF: 0.924

Alfa AF: 0.863 Hom.: 3168

Bravo AF: 0.916

Asia WGS AF: 0.972 AC: 3380 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	0.34
DANN	Benign	0.73

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: rs609004; hg19: chr12-118179710;