5-103155798-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.1404-111A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.273 in 745,772 control chromosomes in the GnomAD database, including 30,396 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.24 (5041 hom., cov: 31)
  • Exomes 𝑓: 0.28 (25355 hom.)
• Consequence: PPIP5K2 NM_001276277.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.130

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=-0.82).
• BP6: Variant 5-103155798-A-G is Benign according to our data. Variant chr5-103155798-A-G is described in ClinVar as [Benign]. Clinvar id is 1237003.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.1404-111A>G		intron_variant		ENST00000358359.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPIP5K2	ENST00000358359.8	c.1404-111A>G		intron_variant		1	NM_001276277.3	P4

Frequencies

GnomAD3 genomes AF: 0.236 AC: 35777 AN: 151770 Hom.: 5044 Cov.: 31

Gnomad AFR AF: 0.0897

Gnomad AMI AF: 0.429

Gnomad AMR AF: 0.229

Gnomad ASJ AF: 0.225

Gnomad EAS AF: 0.449

Gnomad SAS AF: 0.141

Gnomad FIN AF: 0.324

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.301

Gnomad OTH AF: 0.235

GnomAD4 exome AF: 0.283 AC: 167933 AN: 593886 Hom.: 25355 AF XY: 0.277 AC XY: 88034 AN XY: 318022

Gnomad4 AFR exome AF: 0.0890

Gnomad4 AMR exome AF: 0.215

Gnomad4 ASJ exome AF: 0.227

Gnomad4 EAS exome AF: 0.453

Gnomad4 SAS exome AF: 0.145

Gnomad4 FIN exome AF: 0.327

Gnomad4 NFE exome AF: 0.300

Gnomad4 OTH exome AF: 0.268

GnomAD4 genome AF: 0.236 AC: 35787 AN: 151886 Hom.: 5041 Cov.: 31 AF XY: 0.235 AC XY: 17450 AN XY: 74268

Gnomad4 AFR AF: 0.0897

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: 0.234

Alfa AF: 0.275 Hom.: 1431

Bravo AF: 0.223

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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	2.8
Dann	Benign	0.55

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: rs34768; hg19: chr5-102491502; COSMIC: COSV58604008;