Genetic Variant NM_005028.5:c.752A>T (chr10-22550699-T-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_005028.5(PIP4K2A):c.752A>T(p.Asn251Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PIP4K2A
NM_005028.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.89

Publications

62 publications found

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]

PIP4K2A links:

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ACMG classification

Classification was made for transcript

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=0.29186076).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIP4K2A	NM_005028.5 link	c.752A>T	p.Asn251Ile	missense_variant	Exon 7 of 10	ENST00000376573.9	NP_005019.2	P48426-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PIP4K2A	ENST00000376573.9 link	c.752A>T	p.Asn251Ile	missense_variant	Exon 7 of 10	1	NM_005028.5	ENSP00000365757.4	P48426-1
PIP4K2A	ENST00000545335.5 link	c.575A>T	p.Asn192Ile	missense_variant	Exon 7 of 10	2		ENSP00000442098.1	P48426-2
PIP4K2A	ENST00000323883.11 link	c.332A>T	p.Asn111Ile	missense_variant	Exon 5 of 8	2		ENSP00000326294.7	H7BXS3
PIP4K2A	ENST00000604912.1 link	c.290A>T	p.Asn97Ile	missense_variant	Exon 4 of 5	2		ENSP00000473858.1	S4R320

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1451686

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

722760

African (AFR)

AF:

0.00

AC:

AN:

33384

American (AMR)

AF:

0.00

AC:

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26052

East Asian (EAS)

AF:

0.00

AC:

AN:

39634

South Asian (SAS)

AF:

0.00

AC:

AN:

86094

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53408

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5750

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1102602

Other (OTH)

AF:

0.00

AC:

AN:

60046

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

27865

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Uncertain

0.053

BayesDel_noAF

Benign

-0.16

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.065

T;.;.;T

Eigen

Benign

0.0070

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.85

D;D;D;D

M_CAP

Benign

0.018

MetaRNN

Benign

0.29

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.92

L;.;.;.

PhyloP100

5.9

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-1.9

N;N;N;.

REVEL

Benign

0.14

Sift

Benign

0.19

T;T;T;.

Sift4G

Benign

0.19

T;T;T;T

Polyphen

0.0090

B;.;.;.

Vest4

0.75

MutPred

0.34

Loss of ubiquitination at K252 (P = 0.0426);.;.;.;

MVP

0.30

MPC

0.51

ClinPred

0.64

GERP RS

6.1

Varity_R

0.76

gMVP

0.67

Mutation Taster

=24/76

disease causing

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over