5-103147827-T-A

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.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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.108

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=-0.7).
• 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/exons	MANE	UniProt
PPIP5K2	NM_001276277.3	c.643-104T>A		intron_variant		ENST00000358359.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPIP5K2	ENST00000358359.8	c.643-104T>A		intron_variant		1	NM_001276277.3	P4

Frequencies

GnomAD3 genomes AF: 0.0237 AC: 3601 AN: 151954 Hom.: 152 Cov.: 32

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.: 38 AF XY: 0.00226 AC XY: 642 AN XY: 284616

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.: 32 AF XY: 0.0236 AC XY: 1754 AN XY: 74346

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.: 8

Bravo AF: 0.0273

Asia WGS AF: 0.00578 AC: 20 AN: 3472

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	-0.70
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

Other links and lift over

dbSNP: rs7700471; hg19: chr5-102483531;