5-103152867-T-C

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.1130+118T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.269 in 619,890 control chromosomes in the GnomAD database, including 25,052 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.24 (5060 hom., cov: 32)
  • Exomes 𝑓: 0.28 (19992 hom.)
• Consequence: PPIP5K2 NM_001276277.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0130

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=-0.8).
• BP6: Variant 5-103152867-T-C is Benign according to our data. Variant chr5-103152867-T-C is described in ClinVar as [Benign]. Clinvar id is 1266392.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.434 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPIP5K2	NM_001276277.3	c.1130+118T>C		intron_variant		ENST00000358359.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPIP5K2	ENST00000358359.8	c.1130+118T>C		intron_variant		1	NM_001276277.3	P4

Frequencies

GnomAD3 genomes AF: 0.238 AC: 36097 AN: 151654 Hom.: 5063 Cov.: 32

Gnomad AFR AF: 0.0990

Gnomad AMI AF: 0.429

Gnomad AMR AF: 0.229

Gnomad ASJ AF: 0.225

Gnomad EAS AF: 0.449

Gnomad SAS AF: 0.140

Gnomad FIN AF: 0.324

Gnomad MID AF: 0.204

Gnomad NFE AF: 0.301

Gnomad OTH AF: 0.235

GnomAD4 exome AF: 0.280 AC: 130936 AN: 468118 Hom.: 19992 AF XY: 0.274 AC XY: 67812 AN XY: 247754

Gnomad4 AFR exome AF: 0.0987

Gnomad4 AMR exome AF: 0.202

Gnomad4 ASJ exome AF: 0.220

Gnomad4 EAS exome AF: 0.452

Gnomad4 SAS exome AF: 0.140

Gnomad4 FIN exome AF: 0.325

Gnomad4 NFE exome AF: 0.291

Gnomad4 OTH exome AF: 0.263

GnomAD4 genome AF: 0.238 AC: 36111 AN: 151772 Hom.: 5060 Cov.: 32 AF XY: 0.237 AC XY: 17596 AN XY: 74170

Gnomad4 AFR AF: 0.0991

Gnomad4 AMR AF: 0.229

Gnomad4 ASJ AF: 0.225

Gnomad4 EAS AF: 0.449

Gnomad4 SAS AF: 0.140

Gnomad4 FIN AF: 0.324

Gnomad4 NFE AF: 0.301

Gnomad4 OTH AF: 0.233

Alfa AF: 0.280 Hom.: 4621

Bravo AF: 0.226

Asia WGS AF: 0.256 AC: 884 AN: 3468

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 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	7.5
Dann	Benign	0.59

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: rs27896; hg19: chr5-102488571; COSMIC: COSV58603996; COSMIC: COSV58603996;