chr2-238173566-G-C

Position:

• chr2-238173566-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_030768.3(ILKAP):​c.924C>G​(p.Asp308Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ILKAP NM_030768.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.180

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ILKAP	NM_030768.3	c.924C>G	p.Asp308Glu	missense_variant	10/12	ENST00000254654.8	NP_110395.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ILKAP	ENST00000254654.8	c.924C>G	p.Asp308Glu	missense_variant	10/12	1	NM_030768.3	ENSP00000254654.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 25, 2023

The c.924C>G (p.D308E) alteration is located in exon 10 (coding exon 10) of the ILKAP gene. This alteration results from a C to G substitution at nucleotide position 924, causing the aspartic acid (D) at amino acid position 308 to be replaced by a glutamic acid (E). 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	Pathogenic	0.71
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.077	T;T;.
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.63
FATHMM_MKL	Benign	0.50	D
LIST_S2	Uncertain	0.87	D;D;D
M_CAP	Benign	0.017	T
MetaRNN	Uncertain	0.49	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.75	N;.;.
PrimateAI	Uncertain	0.77	T
PROVEAN	Uncertain	-2.8	D;.;D
REVEL	Benign	0.22
Sift	Benign	0.096	T;.;T
Sift4G	Benign	0.51	T;T;T
Polyphen		0.72	P;.;.
Vest4		0.91
MutPred		0.79		Loss of sheet (P = 0.1398);.;.;
MVP		0.32
MPC		1.4
ClinPred		0.93	D
GERP RS		-5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.44
gMVP		0.70

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-239082207;