Variant chr2-238170635-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_030768.3(ILKAP):c.1080C>T(p.Asp360Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00556 in 1,601,756 control chromosomes in the GnomAD database, including 122 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.014 ( 43 hom., cov: 33)

Exomes 𝑓: 0.0047 ( 79 hom. )

Consequence

ILKAP
NM_030768.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.505

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 made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP6

Variant 2-238170635-G-A is Benign according to our data. Variant chr2-238170635-G-A is described in ClinVar as [Benign]. Clinvar id is 773568.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.505 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0141 (2146/152328) while in subpopulation AFR AF= 0.0425 (1768/41572). AF 95% confidence interval is 0.0409. There are 43 homozygotes in gnomad4. There are 1014 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 2146 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ILKAP	NM_030768.3 link	c.1080C>T	p.Asp360Asp	synonymous_variant	12/12	ENST00000254654.8	NP_110395.1	Q9H0C8
ILKAP	XM_006712784.2 link	c.876C>T	p.Asp292Asp	synonymous_variant	11/11		XP_006712847.1
ILKAP	XM_017005057.2 link	c.720C>T	p.Asp240Asp	synonymous_variant	9/9		XP_016860546.1
ILKAP	XM_017005058.2 link	c.684C>T	p.Asp228Asp	synonymous_variant	8/8		XP_016860547.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ILKAP	ENST00000254654.8 link	c.1080C>T	p.Asp360Asp	synonymous_variant	12/12	1	NM_030768.3	ENSP00000254654.3		Q9H0C8

Frequencies

GnomAD3 genomes

AF:

0.0141

AC:

2140

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0425

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00458

Gnomad ASJ

AF:

0.00461

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00766

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00325

Gnomad OTH

AF:

0.0124

GnomAD3 exomes

AF:

0.00654

AC:

1629

AN:

249132

Hom.:

AF XY:

0.00631

AC XY:

850

AN XY:

134786

show subpopulations

Gnomad AFR exome

AF:

0.0426

Gnomad AMR exome

AF:

0.00328

Gnomad ASJ exome

AF:

0.00462

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0111

Gnomad FIN exome

AF:

0.000557

Gnomad NFE exome

AF:

0.00357

Gnomad OTH exome

AF:

0.00513

GnomAD4 exome

AF:

0.00466

AC:

6759

AN:

1449428

Hom.:

Cov.:

AF XY:

0.00486

AC XY:

3492

AN XY:

718304

show subpopulations

Gnomad4 AFR exome

AF:

0.0436

Gnomad4 AMR exome

AF:

0.00335

Gnomad4 ASJ exome

AF:

0.00558

Gnomad4 EAS exome

AF:

0.0000254

Gnomad4 SAS exome

AF:

0.0117

Gnomad4 FIN exome

AF:

0.000509

Gnomad4 NFE exome

AF:

0.00316

Gnomad4 OTH exome

AF:

0.00618

GnomAD4 genome

AF:

0.0141

AC:

2146

AN:

152328

Hom.:

Cov.:

AF XY:

0.0136

AC XY:

1014

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.0425

Gnomad4 AMR

AF:

0.00457

Gnomad4 ASJ

AF:

0.00461

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00746

Gnomad4 FIN

AF:

0.000377

Gnomad4 NFE

AF:

0.00325

Gnomad4 OTH

AF:

0.0118

Alfa

AF:

0.00596

Hom.:

Bravo

AF:

0.0152

Asia WGS

AF:

0.00606

AC:

AN:

3478

EpiCase

AF:

0.00354

EpiControl

AF:

0.00617

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 26, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

0.59

DANN

Benign

0.93

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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