rs199789449

Positions:

• chr11-6604307-C-G
• chr11-6604307-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_004517.4(ILK):​c.36C>G​(p.Asn12Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ILK NM_004517.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.410

Genes affected

ILK (HGNC:6040): (integrin linked kinase) This gene encodes a protein with a kinase-like domain and four ankyrin-like repeats. The encoded protein associates at the cell membrane with the cytoplasmic domain of beta integrins, where it regulates integrin-mediated signal transduction. Activity of this protein is important in the epithelial to mesenchymal transition, and over-expression of this gene is implicated in tumor growth and metastasis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2013]

(HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ILK	NM_004517.4	c.36C>G	p.Asn12Lys	missense_variant	2/13	ENST00000299421.9	NP_004508.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ILK	ENST00000299421.9	c.36C>G	p.Asn12Lys	missense_variant	2/13	1	NM_004517.4	ENSP00000299421	P1
	ENST00000527191.1	n.114G>C		non_coding_transcript_exon_variant	1/2	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Benign	-0.00028	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.23	T;T;T;.;T;.;.
Eigen	Benign	-0.018
Eigen_PC	Benign	-0.10
FATHMM_MKL	Benign	0.46	N
LIST_S2	Uncertain	0.96	.;D;.;D;D;D;D
M_CAP	Uncertain	0.15	D
MetaRNN	Uncertain	0.62	D;D;D;D;D;D;D
MetaSVM	Benign	-0.44	T
MutationAssessor	Benign	1.6	L;.;L;L;L;.;.
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Pathogenic	0.85	D
PROVEAN	Uncertain	-3.3	D;.;D;D;D;.;.
REVEL	Uncertain	0.43
Sift	Uncertain	0.0060	D;.;D;D;D;.;.
Sift4G	Uncertain	0.014	D;D;D;D;D;D;T
Polyphen		1.0	D;.;D;.;D;.;.
Vest4		0.83
MutPred		0.49		Gain of ubiquitination at N12 (P = 0.0408);Gain of ubiquitination at N12 (P = 0.0408);Gain of ubiquitination at N12 (P = 0.0408);Gain of ubiquitination at N12 (P = 0.0408);Gain of ubiquitination at N12 (P = 0.0408);Gain of ubiquitination at N12 (P = 0.0408);.;
MVP		0.82
MPC		1.1
ClinPred		0.99	D
GERP RS		-1.1
Varity_R		0.72
gMVP		0.79

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

Publications

LitVar

Other links and lift over

dbSNP: rs199789449; hg19: chr11-6625537;