rs2293180

Variant names:

• chr17-27582790-C-A
• rs2293180
• NM_001394583.1:c.665C>A
• KSR1 p.Ala222Asp

Your query was ambiguous. Multiple possible variants found:

• chr17-27582790-C-A
• chr17-27582790-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001394583.1(KSR1):​c.665C>A​(p.Ala222Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,384 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict 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: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: KSR1 NM_001394583.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.584
• Publications: 0 publications found

Genes affected

KSR1 (HGNC:6465): (kinase suppressor of ras 1) Enables 14-3-3 protein binding activity; ATP binding activity; and protein C-terminus binding activity. Involved in positive regulation of MAPK cascade. Located in endoplasmic reticulum and membrane. Part of protein-containing complex. Implicated in breast adenocarcinoma. Biomarker of breast cancer. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08661735).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394583.1. 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
	KSR1	NM_001394583.1	MANE Select	c.665C>A	p.Ala222Asp	missense	Exon 4 of 21	NP_001381512.1	A0A2R8Y5H9
	KSR1	NM_001367810.1		c.665C>A	p.Ala222Asp	missense	Exon 4 of 20	NP_001354739.1
	KSR1	NM_014238.2		c.254C>A	p.Ala85Asp	missense	Exon 5 of 22	NP_055053.1	Q8IVT5-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KSR1	ENST00000644974.2	MANE Select	c.665C>A	p.Ala222Asp	missense	Exon 4 of 21	ENSP00000494552.1	A0A2R8Y5H9
	KSR1	ENST00000644418.1		c.410C>A	p.Ala137Asp	missense	Exon 3 of 19	ENSP00000494039.1	A0A2R8Y4X0
	KSR1	ENST00000398988.7	TSL:5	c.254C>A	p.Ala85Asp	missense	Exon 5 of 22	ENSP00000381958.3	Q8IVT5-4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461384 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 727024

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.00 AC: 0 AN: 44658

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26112

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 86242

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53350

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5750

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111742

Other (OTH) AF: 0.00 AC: 0 AN: 60364

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	15
DANN	Uncertain	0.97
DEOGEN2	Benign	0.30	T
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.71
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.0070	T
MetaRNN	Benign	0.087	T
MetaSVM	Benign	-1.1	T
PhyloP100		0.58
PrimateAI	Benign	0.40	T
REVEL	Benign	0.066
Sift4G	Benign	0.55	T
PromoterAI		0.021	Neutral
gMVP		0.22
Mutation Taster		=90/10	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2293180;

hg19: chr17-25909816;