chr10-97656915-G-A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R288W) has been classified 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
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -5 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018425.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PI4K2A	NM_018425.4	MANE Select	c.863G>A	p.Arg288Gln	missense	Exon 4 of 9	NP_060895.1	Q9BTU6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PI4K2A	ENST00000370631.4	TSL:1 MANE Select	c.863G>A	p.Arg288Gln	missense	Exon 4 of 9	ENSP00000359665.3	Q9BTU6
	ENSG00000249967	ENST00000370649.3	TSL:2	c.773G>A	p.Arg258Gln	missense	Exon 5 of 10	ENSP00000359683.3	E9PAM4
	PI4K2A	ENST00000880060.1		c.863G>A	p.Arg288Gln	missense	Exon 4 of 10	ENSP00000550119.1

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

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000540 AC: 6 AN: 1111986

Other (OTH) AF: 0.0000166 AC: 1 AN: 60394

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.044	D
MetaRNN	Benign	0.37	T
MetaSVM	Benign	-0.65	T
MutationAssessor	Benign	-0.14	N
PhyloP100		5.9
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-0.94	N
REVEL	Uncertain	0.32
Sift	Benign	0.70	T
Sift4G	Benign	0.30	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
Mutation Taster		=44/56	disease causing

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

hg19: chr10-99416672; COSMIC: COSV108201777;