rs1846644

Variant names:

• chr12-117500575-T-C
• rs1846644
• NM_173598.6:c.2220-14884A>G

Variant summary

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

The NM_173598.6(KSR2):​c.2220-14884A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.341 in 152,022 control chromosomes in the GnomAD database, including 9,572 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 0.34 (9572 hom., cov: 32)
• Consequence: KSR2 NM_173598.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.658
• Publications: 6 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=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.52 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KSR2	NM_173598.6	c.2220-14884A>G		intron_variant	Intron 14 of 19	ENST00000339824.7	NP_775869.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KSR2	ENST00000339824.7	c.2220-14884A>G		intron_variant	Intron 14 of 19	5	NM_173598.6	ENSP00000339952.4

Frequencies

GnomAD3 genomes AF: 0.341 AC: 51770 AN: 151904 Hom.: 9566 Cov.: 32

Gnomad AFR AF: 0.190

Gnomad AMI AF: 0.293

Gnomad AMR AF: 0.366

Gnomad ASJ AF: 0.298

Gnomad EAS AF: 0.264

Gnomad SAS AF: 0.537

Gnomad FIN AF: 0.439

Gnomad MID AF: 0.420

Gnomad NFE AF: 0.406

Gnomad OTH AF: 0.350

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

GnomAD4 genome AF: 0.341 AC: 51788 AN: 152022 Hom.: 9572 Cov.: 32 AF XY: 0.345 AC XY: 25669 AN XY: 74300

African (AFR) AF: 0.190 AC: 7873 AN: 41498

American (AMR) AF: 0.367 AC: 5606 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.298 AC: 1034 AN: 3470

East Asian (EAS) AF: 0.264 AC: 1368 AN: 5178

South Asian (SAS) AF: 0.537 AC: 2582 AN: 4810

European-Finnish (FIN) AF: 0.439 AC: 4619 AN: 10510

Middle Eastern (MID) AF: 0.424 AC: 123 AN: 290

European-Non Finnish (NFE) AF: 0.406 AC: 27590 AN: 67962

Other (OTH) AF: 0.345 AC: 727 AN: 2108

Alfa AF: 0.356 Hom.: 3940

Bravo AF: 0.325

Asia WGS AF: 0.363 AC: 1263 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.40
DANN	Benign	0.58
PhyloP100		-0.66
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: rs1846644; hg19: chr12-117938380; COSMIC: COSV108132996;