chr10-22541993-C-G

Variant summary

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

The NM_005028.5(PIP4K2A):ā€‹c.847G>Cā€‹(p.Val283Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,684 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000027 ( 0 hom. )

Consequence

PIP4K2A
NM_005028.5 missense

Scores

1
7
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.57
Variant links:
Genes affected
PIP4K2A (HGNC:8997): (phosphatidylinositol-5-phosphate 4-kinase type 2 alpha) Phosphatidylinositol-5,4-bisphosphate, the precursor to second messengers of the phosphoinositide signal transduction pathways, is thought to be involved in the regulation of secretion, cell proliferation, differentiation, and motility. The protein encoded by this gene is one of a family of enzymes capable of catalyzing the phosphorylation of phosphatidylinositol-5-phosphate on the fourth hydroxyl of the myo-inositol ring to form phosphatidylinositol-5,4-bisphosphate. The amino acid sequence of this enzyme does not show homology to other kinases, but the recombinant protein does exhibit kinase activity. This gene is a member of the phosphatidylinositol-5-phosphate 4-kinase family. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

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
PIP4K2ANM_005028.5 linkuse as main transcriptc.847G>C p.Val283Leu missense_variant 8/10 ENST00000376573.9 NP_005019.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PIP4K2AENST00000376573.9 linkuse as main transcriptc.847G>C p.Val283Leu missense_variant 8/101 NM_005028.5 ENSP00000365757 P1P48426-1
PIP4K2AENST00000545335.5 linkuse as main transcriptc.670G>C p.Val224Leu missense_variant 8/102 ENSP00000442098 P48426-2
PIP4K2AENST00000323883.11 linkuse as main transcriptc.427G>C p.Val143Leu missense_variant 6/82 ENSP00000326294
PIP4K2AENST00000604912.1 linkuse as main transcriptc.385G>C p.Val129Leu missense_variant 5/52 ENSP00000473858

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000797
AC:
2
AN:
250982
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135624
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000176
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000274
AC:
4
AN:
1461684
Hom.:
0
Cov.:
33
AF XY:
0.00000138
AC XY:
1
AN XY:
727152
show subpopulations
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:
0.00000360
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.000111
Hom.:
0
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJul 12, 2023The c.847G>C (p.V283L) alteration is located in exon 8 (coding exon 8) of the PIP4K2A gene. This alteration results from a G to C substitution at nucleotide position 847, causing the valine (V) at amino acid position 283 to be replaced by a leucine (L). 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
Uncertain
0.37
BayesDel_addAF
Uncertain
0.035
T
BayesDel_noAF
Benign
-0.17
CADD
Benign
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.053
T;.;.;T
Eigen
Benign
0.18
Eigen_PC
Uncertain
0.36
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Uncertain
0.91
D;D;D;D
M_CAP
Benign
0.024
T
MetaRNN
Uncertain
0.49
T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.51
N;.;.;.
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Pathogenic
0.88
D
PROVEAN
Benign
-1.2
N;N;N;.
REVEL
Benign
0.20
Sift
Benign
0.063
T;T;T;.
Sift4G
Benign
0.42
T;T;T;T
Polyphen
0.45
B;.;.;.
Vest4
0.79
MutPred
0.58
Gain of catalytic residue at V283 (P = 0.083);.;.;.;
MVP
0.42
MPC
0.58
ClinPred
0.38
T
GERP RS
6.1
Varity_R
0.42
gMVP
0.49

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs61749168; hg19: chr10-22830922; API