chr2-238170635-G-A

Variant names:

• chr2-238170635-G-A
• rs34150107
• NM_030768.3:c.1080C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.505
• Publications: 3 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 2146 AD gene.

Transcripts

RefSeq

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

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ILKAP	ENST00000254654.8	c.1080C>T	p.Asp360Asp	synonymous_variant	Exon 12 of 12	1	NM_030768.3	ENSP00000254654.3

Frequencies

GnomAD3 genomes AF: 0.0141 AC: 2140 AN: 152210 Hom.: 42 Cov.: 33

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

GnomAD2 exomes AF: 0.00654 AC: 1629 AN: 249132 AF XY: 0.00631

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 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.: 79 Cov.: 31 AF XY: 0.00486 AC XY: 3492 AN XY: 718304

African (AFR) AF: 0.0436 AC: 1448 AN: 33216

American (AMR) AF: 0.00335 AC: 148 AN: 44230

Ashkenazi Jewish (ASJ) AF: 0.00558 AC: 145 AN: 25984

East Asian (EAS) AF: 0.0000254 AC: 1 AN: 39366

South Asian (SAS) AF: 0.0117 AC: 1008 AN: 85806

European-Finnish (FIN) AF: 0.000509 AC: 27 AN: 53012

Middle Eastern (MID) AF: 0.0220 AC: 126 AN: 5738

European-Non Finnish (NFE) AF: 0.00316 AC: 3487 AN: 1102338

Other (OTH) AF: 0.00618 AC: 369 AN: 59738

GnomAD4 genome AF: 0.0141 AC: 2146 AN: 152328 Hom.: 43 Cov.: 33 AF XY: 0.0136 AC XY: 1014 AN XY: 74492

African (AFR) AF: 0.0425 AC: 1768 AN: 41572

American (AMR) AF: 0.00457 AC: 70 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00461 AC: 16 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5174

South Asian (SAS) AF: 0.00746 AC: 36 AN: 4828

European-Finnish (FIN) AF: 0.000377 AC: 4 AN: 10624

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.00325 AC: 221 AN: 68034

Other (OTH) AF: 0.0118 AC: 25 AN: 2116

Alfa AF: 0.00548 Hom.: 4

Bravo AF: 0.0152

Asia WGS AF: 0.00606 AC: 21 AN: 3478

EpiCase AF: 0.00354

EpiControl AF: 0.00617

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 26, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.59
DANN	Benign	0.93
PhyloP100		-0.51
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs34150107; hg19: chr2-239079276;