5-103154817-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001276277.3(PPIP5K2):c.1294-17A>G variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0203 in 1,548,880 control chromosomes in the GnomAD database, including 1,092 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.052 (524 hom., cov: 32)
  • Exomes 𝑓: 0.017 (568 hom.)
• Consequence: PPIP5K2 NM_001276277.3 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.607

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=-0.86).
• BP6: Variant 5-103154817-A-G is Benign according to our data. Variant chr5-103154817-A-G is described in ClinVar as [Benign]. Clinvar id is 1265614.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.157 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPIP5K2	NM_001276277.3	c.1294-17A>G		splice_polypyrimidine_tract_variant, intron_variant		ENST00000358359.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPIP5K2	ENST00000358359.8	c.1294-17A>G		splice_polypyrimidine_tract_variant, intron_variant		1	NM_001276277.3	P4

Frequencies

GnomAD3 genomes AF: 0.0520 AC: 7902 AN: 152018 Hom.: 522 Cov.: 32

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0162

Gnomad ASJ AF: 0.00576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00151

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0133

Gnomad OTH AF: 0.0398

GnomAD3 exomes AF: 0.0210 AC: 4269 AN: 202838 Hom.: 227 AF XY: 0.0179 AC XY: 1995 AN XY: 111696

Gnomad AFR exome AF: 0.175

Gnomad AMR exome AF: 0.0112

Gnomad ASJ exome AF: 0.00947

Gnomad EAS exome AF: 0.0000681

Gnomad SAS exome AF: 0.00124

Gnomad FIN exome AF: 0.00293

Gnomad NFE exome AF: 0.0143

Gnomad OTH exome AF: 0.0177

GnomAD4 exome AF: 0.0168 AC: 23524 AN: 1396744 Hom.: 568 Cov.: 29 AF XY: 0.0158 AC XY: 10999 AN XY: 694280

Gnomad4 AFR exome AF: 0.170

Gnomad4 AMR exome AF: 0.0121

Gnomad4 ASJ exome AF: 0.00745

Gnomad4 EAS exome AF: 0.0000523

Gnomad4 SAS exome AF: 0.00123

Gnomad4 FIN exome AF: 0.00348

Gnomad4 NFE exome AF: 0.0151

Gnomad4 OTH exome AF: 0.0194

GnomAD4 genome AF: 0.0521 AC: 7927 AN: 152136 Hom.: 524 Cov.: 32 AF XY: 0.0495 AC XY: 3682 AN XY: 74390

Gnomad4 AFR AF: 0.160

Gnomad4 AMR AF: 0.0162

Gnomad4 ASJ AF: 0.00576

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00124

Gnomad4 FIN AF: 0.00151

Gnomad4 NFE AF: 0.0133

Gnomad4 OTH AF: 0.0394

Alfa AF: 0.0117 Hom.: 15

Bravo AF: 0.0583

Asia WGS AF: 0.00988 AC: 34 AN: 3456

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 22, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	4.9
Dann	Benign	0.44
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs58392548; hg19: chr5-102490521;