10-97640807-C-G

Variant names:

• chr10-97640807-C-G
• rs759390226
• NM_018425.4:c.65C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_018425.4(PI4K2A):​c.65C>G​(p.Ser22Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000757 in 1,321,100 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.6e-7 (0 hom.)
• Consequence: PI4K2A NM_018425.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.76
• 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2852648).

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.65C>G	p.Ser22Trp	missense	Exon 1 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.65C>G	p.Ser22Trp	missense	Exon 1 of 9	ENSP00000359665.3	Q9BTU6
	ENSG00000249967	ENST00000370649.3	TSL:2	c.346-10134C>G		intron	N/A	ENSP00000359683.3	E9PAM4
	PI4K2A	ENST00000880060.1		c.65C>G	p.Ser22Trp	missense	Exon 1 of 10	ENSP00000550119.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.57e-7 AC: 1 AN: 1321100 Hom.: 0 Cov.: 31 AF XY: 0.00000153 AC XY: 1 AN XY: 653376

African (AFR) AF: 0.00 AC: 0 AN: 27308

American (AMR) AF: 0.00 AC: 0 AN: 26850

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21664

East Asian (EAS) AF: 0.00 AC: 0 AN: 31150

South Asian (SAS) AF: 0.00 AC: 0 AN: 69118

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47586

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3680

European-Non Finnish (NFE) AF: 9.61e-7 AC: 1 AN: 1040690

Other (OTH) AF: 0.00 AC: 0 AN: 53054

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.10	T
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.15
FATHMM_MKL	Benign	0.44	N
LIST_S2	Benign	0.78	T
M_CAP	Uncertain	0.17	D
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.34	N
PhyloP100		1.8
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.093
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.039	D
Polyphen		0.95	P
Vest4		0.44
MutPred		0.25		Loss of glycosylation at S22 (P = 0.0013)
MVP		0.39
MPC		1.9
ClinPred		0.74	D
GERP RS		3.2
PromoterAI		-0.00060	Neutral
Varity_R		0.15
gMVP		0.30
Mutation Taster		=87/13	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs759390226; hg19: chr10-99400564;