rs2293180

Variant names:

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

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. 12/18 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).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KSR1	NM_001394583.1	c.665C>A	p.Ala222Asp	missense_variant	Exon 4 of 21	ENST00000644974.2	NP_001381512.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KSR1	ENST00000644974.2	c.665C>A	p.Ala222Asp	missense_variant	Exon 4 of 21		NM_001394583.1	ENSP00000494552.1

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 v4.3

Name	Calibrated prediction	Score	Prediction
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;T;T;T;.;T
M_CAP	Benign	0.0070	T
MetaRNN	Benign	0.087	T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
PhyloP100		0.58
PrimateAI	Benign	0.40	T
REVEL	Benign	0.066
Sift4G	Benign	0.55	.;T;T;T;T;.
Vest4		0.26
MVP		0.20
MPC		0.58
ClinPred		0.067	T
GERP RS		1.2
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

Other links and lift over

dbSNP: rs2293180; hg19: chr17-25909816;