Genetic Variant PPIP5K2:c.643-104T>A (chr5-103147827-T-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001276277.3(PPIP5K2):c.643-104T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00731 in 692,498 control chromosomes in the GnomAD database, including 189 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.024 ( 151 hom., cov: 32)

Exomes 𝑓: 0.0027 ( 38 hom. )

Consequence

PPIP5K2
NM_001276277.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.108

Variant links:

Genes affected

PPIP5K2 (HGNC:29035): (diphosphoinositol pentakisphosphate kinase 2) This gene encodes a member of the histidine acid phosphatase family of proteins. Despite containing a histidine acid phosphatase domain, the encoded protein functions as an inositol pyrophosphate kinase, and is thought to lack phosphatase activity. This kinase activity is the mechanism by which the encoded protein synthesizes high-energy inositol pyrophosphates, which act as signaling molecules that regulate cellular homeostasis and other processes. This gene may be associated with autism spectrum disorder in human patients. [provided by RefSeq, Sep 2016]

PPIP5K2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.7).

BP6

Variant 5-103147827-T-A is Benign according to our data. Variant chr5-103147827-T-A is described in ClinVar as [Benign]. Clinvar id is 1246769.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0801 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPIP5K2	NM_001276277.3 link	c.643-104T>A		intron_variant	Intron 6 of 30	ENST00000358359.8	NP_001263206.1	O43314-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPIP5K2	ENST00000358359.8 link	c.643-104T>A		intron_variant	Intron 6 of 30	1	NM_001276277.3	ENSP00000351126.3		O43314-1

Frequencies

GnomAD3 genomes

AF:

0.0237

AC:

3601

AN:

151954

Hom.:

152

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0824

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00964

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000192

Gnomad OTH

AF:

0.0129

GnomAD4 exome

AF:

0.00268

AC:

1446

AN:

540426

Hom.:

AF XY:

0.00226

AC XY:

642

AN XY:

284616

show subpopulations

Gnomad4 AFR exome

AF:

0.0830

Gnomad4 AMR exome

AF:

0.00465

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000222

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000180

Gnomad4 OTH exome

AF:

0.00630

GnomAD4 genome

AF:

0.0238

AC:

3613

AN:

152072

Hom.:

151

Cov.:

AF XY:

0.0236

AC XY:

1754

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.0824

Gnomad4 AMR

AF:

0.00962

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000192

Gnomad4 OTH

AF:

0.0128

Alfa

AF:

0.0167

Hom.:

Bravo

AF:

0.0273

Asia WGS

AF:

0.00578

AC:

AN:

3472

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

May 14, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

2.0

DANN

Benign

0.74

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over