10-97656365-G-T

Variant names:

• chr10-97656365-G-T
• NM_018425.4:c.717G>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_018425.4(PI4K2A):​c.717G>T​(p.Glu239Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PI4K2A NM_018425.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.79

Genes affected

PI4K2A (HGNC:30031): (phosphatidylinositol 4-kinase type 2 alpha) Phosphatidylinositolpolyphosphates (PtdInsPs) are centrally involved in many biologic processes, ranging from cell growth and organization of the actin cytoskeleton to endo- and exocytosis. PI4KII phosphorylates PtdIns at the D-4 position, an essential step in the biosynthesis of PtdInsPs (Barylko et al., 2001 [PubMed 11244087]).[supplied by OMIM, Mar 2008]

ENSG00000249967 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34045303).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PI4K2A	NM_018425.4	c.717G>T	p.Glu239Asp	missense_variant	Exon 3 of 9	ENST00000370631.4	NP_060895.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PI4K2A	ENST00000370631.4	c.717G>T	p.Glu239Asp	missense_variant	Exon 3 of 9	1	NM_018425.4	ENSP00000359665.3
ENSG00000249967	ENST00000370649.3	c.627G>T	p.Glu209Asp	missense_variant	Exon 4 of 10	2		ENSP00000359683.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 29, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.717G>T (p.E239D) alteration is located in exon 3 (coding exon 3) of the PI4K2A gene. This alteration results from a G to T substitution at nucleotide position 717, causing the glutamic acid (E) at amino acid position 239 to be replaced by an aspartic acid (D). 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	0.60
BayesDel_addAF	Uncertain	0.097	D
BayesDel_noAF	Benign	-0.10
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.20	.;T
Eigen	Benign	0.078
Eigen_PC	Benign	0.089
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.84	T;T
M_CAP	Benign	0.050	D
MetaRNN	Benign	0.34	T;T
MetaSVM	Uncertain	0.29	D
MutationAssessor	Benign	1.6	.;L
PrimateAI	Pathogenic	0.79	T
PROVEAN	Benign	-1.6	N;N
REVEL	Uncertain	0.54
Sift	Benign	0.12	T;T
Sift4G	Benign	0.11	T;T
Polyphen		0.0050	.;B
Vest4		0.42
MutPred		0.45		.;Loss of stability (P = 0.0686);
MVP		0.54
MPC		1.1
ClinPred		0.71	D
GERP RS		2.5
Varity_R		0.20
gMVP		0.77

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: chr10-99416122;