2-238170637-C-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4BS2

The NM_030768.3(ILKAP):c.1078G>A(p.Asp360Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000483 in 1,448,738 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. D360D) has been classified as Benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

ILKAP
NM_030768.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.25

Publications

2 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.31771773).

BS2

High AC in GnomAdExome4 at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ILKAP	NM_030768.3 link	c.1078G>A	p.Asp360Asn	missense_variant	Exon 12 of 12	ENST00000254654.8	NP_110395.1	Q9H0C8
ILKAP	XM_006712784.2 link	c.874G>A	p.Asp292Asn	missense_variant	Exon 11 of 11		XP_006712847.1
ILKAP	XM_017005057.2 link	c.718G>A	p.Asp240Asn	missense_variant	Exon 9 of 9		XP_016860546.1
ILKAP	XM_017005058.2 link	c.682G>A	p.Asp228Asn	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.1078G>A	p.Asp360Asn	missense_variant	Exon 12 of 12	1	NM_030768.3	ENSP00000254654.3		Q9H0C8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000402

AC:

AN:

248994

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000293

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:

0.00000483

AC:

AN:

1448738

Hom.:

Cov.:

AF XY:

0.00000418

AC XY:

AN XY:

717836

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33198

American (AMR)

AF:

0.0000226

AC:

AN:

44192

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25976

East Asian (EAS)

AF:

0.00

AC:

AN:

39346

South Asian (SAS)

AF:

0.00

AC:

AN:

85784

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53002

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5742

European-Non Finnish (NFE)

AF:

0.00000545

AC:

AN:

1101784

Other (OTH)

AF:

0.00

AC:

AN:

59714

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.446

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

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 07, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.1078G>A (p.D360N) 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 1078, causing the aspartic acid (D) at amino acid position 360 to be replaced by an asparagine (N). 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

Benign

0.14

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.55

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.049

T;T

Eigen

Benign

0.079

Eigen_PC

Benign

0.13

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.92

D;D

M_CAP

Benign

0.022

MetaRNN

Benign

0.32

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

L;.

PhyloP100

7.2

PrimateAI

Benign

0.47

PROVEAN

Benign

-2.0

N;.

REVEL

Benign

0.11

Sift

Benign

0.13

T;.

Sift4G

Benign

0.10

T;T

Polyphen

0.61

P;.

Vest4

0.38

MutPred

0.37

Gain of MoRF binding (P = 0.036);.;

MVP

0.62

MPC

1.2

ClinPred

0.78

GERP RS

5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.15

gMVP

0.42

Mutation Taster

=78/22

polymorphism

(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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2-238170637-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over