Genetic Variant NM_005028.5:c.493-101G>T (chr10-22573558-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005028.5(PIP4K2A):c.493-101G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.29 in 1,003,094 control chromosomes in the GnomAD database, including 44,776 homozygotes. 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: 𝑓 0.27 ( 5709 hom., cov: 32)

Exomes 𝑓: 0.29 ( 39067 hom. )

Consequence

PIP4K2A
NM_005028.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.477

Publications

13 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: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.304 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIP4K2A	NM_005028.5 link	c.493-101G>T		intron_variant	Intron 4 of 9	ENST00000376573.9	NP_005019.2	P48426-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIP4K2A	ENST00000376573.9 link	c.493-101G>T		intron_variant	Intron 4 of 9	1	NM_005028.5	ENSP00000365757.4		P48426-1

Frequencies

GnomAD3 genomes

AF:

0.266

AC:

40345

AN:

151952

Hom.:

5704

Cov.:

show subpopulations

Gnomad AFR

AF:

0.251

Gnomad AMI

AF:

0.449

Gnomad AMR

AF:

0.184

Gnomad ASJ

AF:

0.321

Gnomad EAS

AF:

0.0283

Gnomad SAS

AF:

0.204

Gnomad FIN

AF:

0.287

Gnomad MID

AF:

0.166

Gnomad NFE

AF:

0.308

Gnomad OTH

AF:

0.242

GnomAD4 exome

AF:

0.294

AC:

250255

AN:

851022

Hom.:

39067

AF XY:

0.291

AC XY:

124946

AN XY:

429246

show subpopulations

African (AFR)

AF:

0.253

AC:

4893

AN:

19364

American (AMR)

AF:

0.153

AC:

2925

AN:

19156

Ashkenazi Jewish (ASJ)

AF:

0.326

AC:

5337

AN:

16374

East Asian (EAS)

AF:

0.0194

AC:

637

AN:

32864

South Asian (SAS)

AF:

0.216

AC:

11220

AN:

51850

European-Finnish (FIN)

AF:

0.288

AC:

10385

AN:

36074

Middle Eastern (MID)

AF:

0.196

AC:

828

AN:

4224

European-Non Finnish (NFE)

AF:

0.321

AC:

203192

AN:

632032

Other (OTH)

AF:

0.277

AC:

10838

AN:

39084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

8396

16793

25189

33586

41982

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5600

11200

16800

22400

28000

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.266

AC:

40391

AN:

152072

Hom.:

5709

Cov.:

AF XY:

0.258

AC XY:

19206

AN XY:

74342

show subpopulations

African (AFR)

AF:

0.252

AC:

10434

AN:

41460

American (AMR)

AF:

0.184

AC:

2806

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.321

AC:

1116

AN:

3472

East Asian (EAS)

AF:

0.0284

AC:

147

AN:

5178

South Asian (SAS)

AF:

0.204

AC:

985

AN:

4828

European-Finnish (FIN)

AF:

0.287

AC:

3028

AN:

10558

Middle Eastern (MID)

AF:

0.167

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.308

AC:

20903

AN:

67976

Other (OTH)

AF:

0.244

AC:

514

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

1510

3019

4529

6038

7548

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

416

832

1248

1664

2080

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.282

Hom.:

4274

Bravo

AF:

0.257

Asia WGS

AF:

0.126

AC:

437

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

4.1

(source)

DANN

Benign

0.64

PhyloP100

-0.48

Mutation Taster

=100/0

polymorphism (auto)

(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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over