5-103151384-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001276277.3(PPIP5K2):c.1028+10T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00227 in 1,583,028 control chromosomes in the GnomAD database, including 62 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.012 (35 hom., cov: 32)
  • Exomes 𝑓: 0.0012 (27 hom.)
• Consequence: PPIP5K2 NM_001276277.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.43

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 5-103151384-T-G is Benign according to our data. Variant chr5-103151384-T-G is described in ClinVar as [Benign]. Clinvar id is 3038048.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0123 (1867/152248) while in subpopulation AFR AF= 0.0435 (1807/41558). AF 95% confidence interval is 0.0418. There are 35 homozygotes in gnomad4. There are 892 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 35 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPIP5K2	NM_001276277.3	c.1028+10T>G		intron_variant		ENST00000358359.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPIP5K2	ENST00000358359.8	c.1028+10T>G		intron_variant		1	NM_001276277.3	P4

Frequencies

GnomAD3 genomes AF: 0.0122 AC: 1858 AN: 152130 Hom.: 35 Cov.: 32

Gnomad AFR AF: 0.0434

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00670

GnomAD3 exomes AF: 0.00303 AC: 708 AN: 233354 Hom.: 17 AF XY: 0.00208 AC XY: 264 AN XY: 126676

Gnomad AFR exome AF: 0.0424

Gnomad AMR exome AF: 0.00161

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000753

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000644

Gnomad OTH exome AF: 0.000716

GnomAD4 exome AF: 0.00121 AC: 1731 AN: 1430780 Hom.: 27 Cov.: 28 AF XY: 0.00106 AC XY: 753 AN XY: 712444

Gnomad4 AFR exome AF: 0.0438

Gnomad4 AMR exome AF: 0.00176

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000195

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000630

Gnomad4 OTH exome AF: 0.00286

GnomAD4 genome AF: 0.0123 AC: 1867 AN: 152248 Hom.: 35 Cov.: 32 AF XY: 0.0120 AC XY: 892 AN XY: 74456

Gnomad4 AFR AF: 0.0435

Gnomad4 AMR AF: 0.00262

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000883

Gnomad4 OTH AF: 0.00664

Alfa AF: 0.00579 Hom.: 2

Bravo AF: 0.0139

Asia WGS AF: 0.00318 AC: 11 AN: 3470

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

PPIP5K2-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 23, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	12
Dann	Benign	0.69

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

Other links and lift over

dbSNP: rs74430672; hg19: chr5-102487088;