dbSNP rs145213569: ILK:p.Phe5Leu (chr11-6604286-C-A) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_004517.4(ILK):c.15C>A(p.Phe5Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. F5F) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ILK
NM_004517.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.02

Publications

0 publications found

Variant links:

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]

ILK Gene-Disease associations (from GenCC):

dilated cardiomyopathy
Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ILK links:

ENSG00000254400 (HGNC:):

ENSG00000254400 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.778

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ILK	NM_004517.4 link	c.15C>A	p.Phe5Leu	missense_variant	Exon 2 of 13	ENST00000299421.9	NP_004508.1	Q13418-1V9HWF0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ILK	ENST00000299421.9 link	c.15C>A	p.Phe5Leu	missense_variant	Exon 2 of 13	1	NM_004517.4	ENSP00000299421.4		Q13418-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1460140

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726254

African (AFR)

AF:

0.00

AC:

AN:

33444

American (AMR)

AF:

0.00

AC:

AN:

44626

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26102

East Asian (EAS)

AF:

0.00

AC:

AN:

39670

South Asian (SAS)

AF:

0.00

AC:

AN:

85974

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52848

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5544

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111616

Other (OTH)

AF:

0.00

AC:

AN:

60316

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

1.0

BayesDel_addAF

Pathogenic

0.32

BayesDel_noAF

Pathogenic

0.22

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.35

T;T;T;.;T;.

Eigen

Benign

0.17

Eigen_PC

Benign

0.19

FATHMM_MKL

Benign

0.54

LIST_S2

Uncertain

0.95

.;D;.;D;D;D

M_CAP

Uncertain

0.12

MetaRNN

Pathogenic

0.78

D;D;D;D;D;D

MetaSVM

Benign

-0.41

MutationAssessor

Benign

1.6

L;.;L;L;L;.

PhyloP100

1.0

PrimateAI

Pathogenic

0.92

PROVEAN

Uncertain

-2.8

D;.;D;D;D;.

REVEL

Uncertain

0.57

Sift

Uncertain

0.0070

D;.;D;D;D;.

Sift4G

Benign

0.061

T;D;T;D;T;D

Polyphen

0.98

D;.;D;.;D;.

Vest4

0.91

MutPred

0.54

Gain of disorder (P = 0.1561);Gain of disorder (P = 0.1561);Gain of disorder (P = 0.1561);Gain of disorder (P = 0.1561);Gain of disorder (P = 0.1561);Gain of disorder (P = 0.1561);

MVP

0.90

MPC

1.1

ClinPred

0.98

GERP RS

3.2

PromoterAI

0.0086

Neutral

(source)

Varity_R

0.73

gMVP

0.71

Mutation Taster

=28/72

disease causing

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over