12-117553742-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.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

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.392 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KSR2	NM_173598.6	c.1518+1427G>A		intron_variant		ENST00000339824.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KSR2	ENST00000339824.7	c.1518+1427G>A		intron_variant		5	NM_173598.6	P1
KSR2	ENST00000543793.1	n.61+1427G>A		intron_variant, non_coding_transcript_variant		3
KSR2	ENST00000545002.1	n.664+1427G>A		intron_variant, non_coding_transcript_variant		2

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

Gnomad4 AFR AF: 0.212

Gnomad4 AMR AF: 0.368

Gnomad4 ASJ AF: 0.507

Gnomad4 EAS AF: 0.407

Gnomad4 SAS AF: 0.229

Gnomad4 FIN AF: 0.387

Gnomad4 NFE AF: 0.335

Gnomad4 OTH AF: 0.313

Alfa AF: 0.328 Hom.: 12369

Bravo AF: 0.308

Asia WGS AF: 0.308 AC: 1069 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	1.6
Dann	Benign	0.63

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: rs708857; hg19: chr12-117991547;