Variant chr2-238170625-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_030768.3(ILKAP):c.1090G>A(p.Glu364Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000108 in 1,604,074 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00012 ( 0 hom. )

Consequence

ILKAP
NM_030768.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.25

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAd4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ILKAP	NM_030768.3 link	c.1090G>A	p.Glu364Lys	missense_variant	12/12	ENST00000254654.8	NP_110395.1	Q9H0C8
ILKAP	XM_006712784.2 link	c.886G>A	p.Glu296Lys	missense_variant	11/11		XP_006712847.1
ILKAP	XM_017005057.2 link	c.730G>A	p.Glu244Lys	missense_variant	9/9		XP_016860546.1
ILKAP	XM_017005058.2 link	c.694G>A	p.Glu232Lys	missense_variant	8/8		XP_016860547.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ILKAP	ENST00000254654.8 link	c.1090G>A	p.Glu364Lys	missense_variant	12/12	1	NM_030768.3	ENSP00000254654.3		Q9H0C8

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000360

AC:

AN:

249974

Hom.:

AF XY:

0.0000296

AC XY:

AN XY:

135238

show subpopulations

Gnomad AFR exome

AF:

0.0000619

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000329

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000619

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000115

AC:

167

AN:

1451866

Hom.:

Cov.:

AF XY:

0.000118

AC XY:

AN XY:

720014

show subpopulations

Gnomad4 AFR exome

AF:

0.0000300

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000147

Gnomad4 OTH exome

AF:

0.0000501

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152208

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.0000724

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000847

Hom.:

Bravo

AF:

0.0000302

ExAC

AF:

0.0000412

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 15, 2021

The c.1090G>A (p.E364K) alteration is located in exon 12 (coding exon 12) of the ILKAP gene. This alteration results from a G to A substitution at nucleotide position 1090, causing the glutamic acid (E) at amino acid position 364 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.46

BayesDel_addAF

Uncertain

0.047

BayesDel_noAF

Uncertain

0.010

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.042

T;T

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.95

D;D

M_CAP

Benign

0.041

MetaRNN

Uncertain

0.72

D;D

MetaSVM

Benign

-1.2

MutationAssessor

Benign

1.6

L;.

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-1.8

N;.

REVEL

Uncertain

0.30

Sift

Benign

0.083

T;.

Sift4G

Benign

0.061

T;T

Polyphen

0.66

P;.

Vest4

0.87

MutPred

0.60

Gain of MoRF binding (P = 0.002);.;

MVP

0.66

MPC

1.5

ClinPred

0.32

GERP RS

5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.35

gMVP

0.76

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over