dbSNP rs750957488: ILKAP:p.Thr352Ile (chr2-238170660-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_030768.3(ILKAP):c.1055C>T(p.Thr352Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000692 in 1,445,186 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T352N) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

ILKAP
NM_030768.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.188

Publications

0 publications found

Variant links:

Genes affected

ILKAP (HGNC:15566): (ILK associated serine/threonine phosphatase) The protein encoded by this gene is a protein serine/threonine phosphatase of the PP2C family. This protein can interact with integrin-linked kinase (ILK/ILK1), a regulator of integrin mediated signaling, and regulate the kinase activity of ILK. Through the interaction with ILK, this protein may selectively affect the signaling process of ILK-mediated glycogen synthase kinase 3 beta (GSK3beta), and thus participate in Wnt signaling pathway. [provided by RefSeq, Jul 2008]

ILKAP links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.058284163).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ILKAP	NM_030768.3 link	c.1055C>T	p.Thr352Ile	missense_variant	Exon 12 of 12	ENST00000254654.8	NP_110395.1	Q9H0C8
ILKAP	XM_006712784.2 link	c.851C>T	p.Thr284Ile	missense_variant	Exon 11 of 11		XP_006712847.1
ILKAP	XM_017005057.2 link	c.695C>T	p.Thr232Ile	missense_variant	Exon 9 of 9		XP_016860546.1
ILKAP	XM_017005058.2 link	c.659C>T	p.Thr220Ile	missense_variant	Exon 8 of 8		XP_016860547.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ILKAP	ENST00000254654.8 link	c.1055C>T	p.Thr352Ile	missense_variant	Exon 12 of 12	1	NM_030768.3	ENSP00000254654.3		Q9H0C8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000403

AC:

AN:

247856

AF XY:

0.00000746

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.92e-7

AC:

AN:

1445186

Hom.:

Cov.:

AF XY:

0.00000140

AC XY:

AN XY:

715384

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33162

American (AMR)

AF:

0.00

AC:

AN:

44096

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25822

East Asian (EAS)

AF:

0.00

AC:

AN:

39278

South Asian (SAS)

AF:

0.0000117

AC:

AN:

85602

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52930

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5718

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1099034

Other (OTH)

AF:

0.00

AC:

AN:

59544

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.675

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.70

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.037

T;T

Eigen

Benign

-0.58

Eigen_PC

Benign

-0.47

FATHMM_MKL

Benign

0.27

LIST_S2

Benign

0.81

T;T

M_CAP

Benign

0.010

MetaRNN

Benign

0.058

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.080

N;.

PhyloP100

-0.19

PrimateAI

Benign

0.38

PROVEAN

Benign

-1.6

N;.

REVEL

Benign

0.041

Sift

Benign

0.16

T;.

Sift4G

Benign

0.19

T;T

Polyphen

0.015

B;.

Vest4

0.086

MutPred

0.37

Loss of phosphorylation at T352 (P = 0.036);.;

MVP

0.15

MPC

0.77

ClinPred

0.14

GERP RS

2.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.066

gMVP

0.26

Mutation Taster

=88/12

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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