rs373511769

Variant names:

• chr12-117467158-C-A
• rs373511769
• NM_173598.6:c.*41G>T

Your query was ambiguous. Multiple possible variants found:

• chr12-117467158-C-A
• chr12-117467158-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_173598.6(KSR2):​c.*41G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000191 in 524,454 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000019 (0 hom.)
• Consequence: KSR2 NM_173598.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173598.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KSR2	NM_173598.6	MANE Select	c.*41G>T		3_prime_UTR	Exon 20 of 20	NP_775869.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KSR2	ENST00000339824.7	TSL:5 MANE Select	c.*41G>T		3_prime_UTR	Exon 20 of 20	ENSP00000339952.4	Q6VAB6-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000191 AC: 1 AN: 524454 Hom.: 0 Cov.: 0 AF XY: 0.00000349 AC XY: 1 AN XY: 286324

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 12512

American (AMR) AF: 0.00 AC: 0 AN: 27196

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15458

East Asian (EAS) AF: 0.00 AC: 0 AN: 30402

South Asian (SAS) AF: 0.0000193 AC: 1 AN: 51740

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50282

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3516

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 304912

Other (OTH) AF: 0.00 AC: 0 AN: 28436

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	5.3
DANN	Benign	0.73
PhyloP100		-1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs373511769; hg19: chr12-117904963;