10-97656915-G-A

Variant names:

• chr10-97656915-G-A
• NM_018425.4:c.863G>A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4 BS2

The NM_018425.4(PI4K2A):​c.863G>A​(p.Arg288Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000479 in 1,461,860 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: PI4K2A NM_018425.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.93

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 Likely_benign. Variant got -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.36685723).
• BS2: High AC in GnomAdExome4 at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PI4K2A	NM_018425.4	c.863G>A	p.Arg288Gln	missense_variant	Exon 4 of 9	ENST00000370631.4	NP_060895.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PI4K2A	ENST00000370631.4	c.863G>A	p.Arg288Gln	missense_variant	Exon 4 of 9	1	NM_018425.4	ENSP00000359665.3
ENSG00000249967	ENST00000370649.3	c.773G>A	p.Arg258Gln	missense_variant	Exon 5 of 10	2		ENSP00000359683.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1461860 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727228

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000540

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 18, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.863G>A (p.R288Q) alteration is located in exon 4 (coding exon 4) of the PI4K2A gene. This alteration results from a G to A substitution at nucleotide position 863, causing the arginine (R) at amino acid position 288 to be replaced by a glutamine (Q). 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	0.079
BayesDel_addAF	Uncertain	0.035	T
BayesDel_noAF	Benign	-0.19
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.089	.;T
Eigen	Benign	0.068
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.89	D;D
M_CAP	Benign	0.044	D
MetaRNN	Benign	0.37	T;T
MetaSVM	Benign	-0.65	T
MutationAssessor	Benign	-0.14	.;N
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-0.94	N;N
REVEL	Uncertain	0.32
Sift	Benign	0.70	T;T
Sift4G	Benign	0.30	T;T
Polyphen		0.17	.;B
Vest4		0.63
MutPred		0.38		.;Loss of helix (P = 0.0558);
MVP		0.47
MPC		1.3
ClinPred		0.95	D
GERP RS		5.3
Varity_R		0.46
gMVP		0.72

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: chr10-99416672;