rs2723279

chr12-117835066-C-A

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KSR2	NM_173598.6	c.472+20362G>T		intron_variant		ENST00000339824.7
LOC105370011	XR_945403.3	n.157+829C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KSR2	ENST00000339824.7	c.472+20362G>T		intron_variant		5	NM_173598.6	P1

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

Gnomad4 AFR AF: 0.387

Gnomad4 AMR AF: 0.386

Gnomad4 ASJ AF: 0.186

Gnomad4 EAS AF: 0.339

Gnomad4 SAS AF: 0.233

Gnomad4 FIN AF: 0.336

Gnomad4 NFE AF: 0.299

Gnomad4 OTH AF: 0.280

Alfa AF: 0.292 Hom.: 8846

Bravo AF: 0.336

Asia WGS AF: 0.279 AC: 972 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.58
Dann	Benign	0.51

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: rs2723279; hg19: chr12-118272871;