chr12-117835066-C-A

Variant names:

• chr12-117835066-C-A
• rs2723279
• NM_173598.6:c.472+20362G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_173598.6(KSR2):​c.472+20362G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.33 in 151,836 control chromosomes in the GnomAD database, including 8,627 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 0.33 (8627 hom., cov: 31)
• Consequence: KSR2 NM_173598.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.873
• Publications: 2 publications found

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]

LOC105370011 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.382 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173598.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KSR2	NM_173598.6	MANE Select	c.472+20362G>T		intron	N/A	NP_775869.4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KSR2	ENST00000339824.7	TSL:5 MANE Select	c.472+20362G>T		intron	N/A	ENSP00000339952.4

Frequencies

GnomAD3 genomes AF: 0.330 AC: 50073 AN: 151720 Hom.: 8620 Cov.: 31

Gnomad AFR AF: 0.387

Gnomad AMI AF: 0.230

Gnomad AMR AF: 0.386

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.339

Gnomad SAS AF: 0.233

Gnomad FIN AF: 0.336

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.299

Gnomad OTH AF: 0.279

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

GnomAD4 genome AF: 0.330 AC: 50108 AN: 151836 Hom.: 8627 Cov.: 31 AF XY: 0.332 AC XY: 24610 AN XY: 74192

African (AFR) AF: 0.387 AC: 16022 AN: 41388

American (AMR) AF: 0.386 AC: 5889 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.186 AC: 644 AN: 3470

East Asian (EAS) AF: 0.339 AC: 1740 AN: 5128

South Asian (SAS) AF: 0.233 AC: 1119 AN: 4794

European-Finnish (FIN) AF: 0.336 AC: 3538 AN: 10544

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.299 AC: 20291 AN: 67930

Other (OTH) AF: 0.280 AC: 591 AN: 2108

Alfa AF: 0.296 Hom.: 12083

Bravo AF: 0.336

Asia WGS AF: 0.279 AC: 972 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.58
DANN	Benign	0.51
PhyloP100		-0.87
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2723279; hg19: chr12-118272871;