rs656255

Positions:

• chr12-117684843-A-C

Variant summary

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

The NM_173598.6(KSR2):​c.987-17185T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.443 in 152,092 control chromosomes in the GnomAD database, including 15,834 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 0.44 (15834 hom., cov: 32)
• Consequence: KSR2 NM_173598.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.362

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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.54 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KSR2	NM_173598.6	c.987-17185T>G		intron_variant		ENST00000339824.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KSR2	ENST00000339824.7	c.987-17185T>G		intron_variant		5	NM_173598.6	P1

Frequencies

GnomAD3 genomes AF: 0.443 AC: 67328 AN: 151976 Hom.: 15824 Cov.: 32

Gnomad AFR AF: 0.288

Gnomad AMI AF: 0.452

Gnomad AMR AF: 0.422

Gnomad ASJ AF: 0.562

Gnomad EAS AF: 0.366

Gnomad SAS AF: 0.558

Gnomad FIN AF: 0.495

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.525

Gnomad OTH AF: 0.456

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

GnomAD4 genome AF: 0.443 AC: 67368 AN: 152092 Hom.: 15834 Cov.: 32 AF XY: 0.445 AC XY: 33064 AN XY: 74334

Gnomad4 AFR AF: 0.288

Gnomad4 AMR AF: 0.422

Gnomad4 ASJ AF: 0.562

Gnomad4 EAS AF: 0.366

Gnomad4 SAS AF: 0.557

Gnomad4 FIN AF: 0.495

Gnomad4 NFE AF: 0.525

Gnomad4 OTH AF: 0.462

Alfa AF: 0.507 Hom.: 11031

Bravo AF: 0.424

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.3
DANN	Benign	0.41

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: rs656255; hg19: chr12-118122648;