rs10431397

Variant names:

• chr12-117668389-C-T
• rs10431397
• NM_173598.6:c.987-731G>A

Variant summary

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

The NM_173598.6(KSR2):​c.987-731G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0603 in 152,232 control chromosomes in the GnomAD database, including 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 0.060 (667 hom., cov: 32)
• Consequence: KSR2 NM_173598.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0260
• Publications: 5 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.172 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KSR2	NM_173598.6	c.987-731G>A		intron_variant	Intron 4 of 19	ENST00000339824.7	NP_775869.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KSR2	ENST00000339824.7	c.987-731G>A		intron_variant	Intron 4 of 19	5	NM_173598.6	ENSP00000339952.4
KSR2	ENST00000545002.1	n.133-731G>A		intron_variant	Intron 2 of 12	2

Frequencies

GnomAD3 genomes AF: 0.0604 AC: 9182 AN: 152114 Hom.: 669 Cov.: 32

Gnomad AFR AF: 0.175

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0274

Gnomad ASJ AF: 0.00519

Gnomad EAS AF: 0.0592

Gnomad SAS AF: 0.00910

Gnomad FIN AF: 0.00669

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0140

Gnomad OTH AF: 0.0498

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

GnomAD4 genome AF: 0.0603 AC: 9184 AN: 152232 Hom.: 667 Cov.: 32 AF XY: 0.0596 AC XY: 4439 AN XY: 74440

African (AFR) AF: 0.175 AC: 7261 AN: 41520

American (AMR) AF: 0.0274 AC: 419 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00519 AC: 18 AN: 3470

East Asian (EAS) AF: 0.0591 AC: 305 AN: 5160

South Asian (SAS) AF: 0.00828 AC: 40 AN: 4830

European-Finnish (FIN) AF: 0.00669 AC: 71 AN: 10618

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0140 AC: 955 AN: 68020

Other (OTH) AF: 0.0492 AC: 104 AN: 2112

Alfa AF: 0.0315 Hom.: 637

Bravo AF: 0.0692

Asia WGS AF: 0.0390 AC: 135 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.3
DANN	Benign	0.78
PhyloP100		-0.026
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs10431397; hg19: chr12-118106194;