rs774644548

Variant names:

• chr12-117467212-T-A
• rs774644548
• NM_173598.6:c.2847-7A>T

Your query was ambiguous. Multiple possible variants found:

• chr12-117467212-T-A
• chr12-117467212-T-C

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.2847-7A>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000174 in 573,968 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000017 (0 hom.)
• Consequence: KSR2 NM_173598.6 splice_region, intron
• Scores: Splicing: ADA: 0.00001556
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.05
• 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=-0.74).

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.2847-7A>T		splice_region intron	N/A	NP_775869.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KSR2	ENST00000339824.7	TSL:5 MANE Select	c.2847-7A>T		splice_region intron	N/A	ENSP00000339952.4	Q6VAB6-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000174 AC: 1 AN: 573968 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 314418

African (AFR) AF: 0.00 AC: 0 AN: 14240

American (AMR) AF: 0.00 AC: 0 AN: 35228

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18672

East Asian (EAS) AF: 0.00 AC: 0 AN: 31458

South Asian (SAS) AF: 0.00 AC: 0 AN: 61948

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52034

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3922

European-Non Finnish (NFE) AF: 0.00000307 AC: 1 AN: 325910

Other (OTH) AF: 0.00 AC: 0 AN: 30556

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.094
DANN	Benign	0.76
PhyloP100		-2.0

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000016
dbscSNV1_RF	Benign	0.0
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: rs774644548; hg19: chr12-117905017;