12-117553742-C-T

Variant names:

• chr12-117553742-C-T
• rs708857
• NM_173598.6:c.1518+1427G>A

Variant summary

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

The NM_173598.6(KSR2):​c.1518+1427G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 151,614 control chromosomes in the GnomAD database, including 7,667 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 0.31 (7667 hom., cov: 31)
• Consequence: KSR2 NM_173598.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.510
• 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.392 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KSR2	NM_173598.6	MANE Select	c.1518+1427G>A		intron	N/A	NP_775869.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KSR2	ENST00000339824.7	TSL:5 MANE Select	c.1518+1427G>A		intron	N/A	ENSP00000339952.4
	KSR2	ENST00000543793.1	TSL:3	n.61+1427G>A		intron	N/A
	KSR2	ENST00000545002.1	TSL:2	n.664+1427G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.310 AC: 47025 AN: 151496 Hom.: 7657 Cov.: 31

Gnomad AFR AF: 0.211

Gnomad AMI AF: 0.292

Gnomad AMR AF: 0.368

Gnomad ASJ AF: 0.507

Gnomad EAS AF: 0.406

Gnomad SAS AF: 0.229

Gnomad FIN AF: 0.387

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.335

Gnomad OTH AF: 0.310

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

GnomAD4 genome AF: 0.311 AC: 47077 AN: 151614 Hom.: 7667 Cov.: 31 AF XY: 0.313 AC XY: 23165 AN XY: 74000

African (AFR) AF: 0.212 AC: 8758 AN: 41372

American (AMR) AF: 0.368 AC: 5613 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.507 AC: 1754 AN: 3462

East Asian (EAS) AF: 0.407 AC: 2087 AN: 5134

South Asian (SAS) AF: 0.229 AC: 1102 AN: 4802

European-Finnish (FIN) AF: 0.387 AC: 4037 AN: 10434

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.335 AC: 22702 AN: 67862

Other (OTH) AF: 0.313 AC: 658 AN: 2104

Alfa AF: 0.322 Hom.: 17530

Bravo AF: 0.308

Asia WGS AF: 0.308 AC: 1069 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.6
DANN	Benign	0.63
PhyloP100		-0.51
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: rs708857; hg19: chr12-117991547;