12-117916066-A-C

Variant names:

• chr12-117916066-A-C
• rs10444502
• NM_173598.6:c.180+52010T>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.180+52010T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.405 in 150,918 control chromosomes in the GnomAD database, including 13,386 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 0.41 (13386 hom., cov: 29)
• Consequence: KSR2 NM_173598.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.563
• 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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.683 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KSR2	NM_173598.6	c.180+52010T>G		intron_variant	Intron 1 of 19	ENST00000339824.7	NP_775869.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KSR2	ENST00000339824.7	c.180+52010T>G		intron_variant	Intron 1 of 19	5	NM_173598.6	ENSP00000339952.4

Frequencies

GnomAD3 genomes AF: 0.405 AC: 61107 AN: 150804 Hom.: 13342 Cov.: 29

Gnomad AFR AF: 0.514

Gnomad AMI AF: 0.449

Gnomad AMR AF: 0.462

Gnomad ASJ AF: 0.394

Gnomad EAS AF: 0.702

Gnomad SAS AF: 0.501

Gnomad FIN AF: 0.311

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.314

Gnomad OTH AF: 0.376

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

GnomAD4 genome AF: 0.405 AC: 61196 AN: 150918 Hom.: 13386 Cov.: 29 AF XY: 0.410 AC XY: 30174 AN XY: 73610

African (AFR) AF: 0.514 AC: 21016 AN: 40892

American (AMR) AF: 0.462 AC: 6989 AN: 15116

Ashkenazi Jewish (ASJ) AF: 0.394 AC: 1363 AN: 3460

East Asian (EAS) AF: 0.702 AC: 3614 AN: 5148

South Asian (SAS) AF: 0.500 AC: 2389 AN: 4774

European-Finnish (FIN) AF: 0.311 AC: 3211 AN: 10314

Middle Eastern (MID) AF: 0.333 AC: 98 AN: 294

European-Non Finnish (NFE) AF: 0.314 AC: 21300 AN: 67910

Other (OTH) AF: 0.384 AC: 807 AN: 2100

Alfa AF: 0.350 Hom.: 42841

Bravo AF: 0.424

Asia WGS AF: 0.636 AC: 2211 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.2
DANN	Benign	0.57
PhyloP100		-0.56
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: rs10444502; hg19: chr12-118353871;