rs199789449

Variant names:

• chr11-6604307-C-G
• rs199789449
• NM_004517.4:c.36C>G

Your query was ambiguous. Multiple possible variants found:

• 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ILK NM_004517.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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]

ENSG00000254400 (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 rank	MANE	Protein	UniProt
ILK	NM_004517.4	c.36C>G	p.Asn12Lys	missense_variant	Exon 2 of 13	ENST00000299421.9	NP_004508.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ILK	ENST00000299421.9	c.36C>G	p.Asn12Lys	missense_variant	Exon 2 of 13	1	NM_004517.4	ENSP00000299421.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Primary familial hypertrophic cardiomyopathy Uncertain:1

Jul 01, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This sequence change replaces asparagine, which is neutral and polar, with lysine, which is basic and polar, at codon 12 of the ILK protein (p.Asn12Lys). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with ILK-related conditions. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

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;.;.
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;