5-103151019-G-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.907-234G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.32 in 151,166 control chromosomes in the GnomAD database, including 7,985 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.32 (7985 hom., cov: 30)
• Consequence: PPIP5K2 NM_001276277.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.387

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=-0.9).
• BP6: Variant 5-103151019-G-C is Benign according to our data. Variant chr5-103151019-G-C is described in ClinVar as [Benign]. Clinvar id is 1267245.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.435 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPIP5K2	NM_001276277.3	c.907-234G>C		intron_variant		ENST00000358359.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPIP5K2	ENST00000358359.8	c.907-234G>C		intron_variant		1	NM_001276277.3	P4

Frequencies

GnomAD3 genomes AF: 0.320 AC: 48289 AN: 151056 Hom.: 7966 Cov.: 30

Gnomad AFR AF: 0.360

Gnomad AMI AF: 0.431

Gnomad AMR AF: 0.257

Gnomad ASJ AF: 0.231

Gnomad EAS AF: 0.450

Gnomad SAS AF: 0.144

Gnomad FIN AF: 0.329

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.315

Gnomad OTH AF: 0.291

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.320 AC: 48352 AN: 151166 Hom.: 7985 Cov.: 30 AF XY: 0.317 AC XY: 23388 AN XY: 73806

Gnomad4 AFR AF: 0.361

Gnomad4 AMR AF: 0.257

Gnomad4 ASJ AF: 0.231

Gnomad4 EAS AF: 0.450

Gnomad4 SAS AF: 0.143

Gnomad4 FIN AF: 0.329

Gnomad4 NFE AF: 0.315

Gnomad4 OTH AF: 0.289

Alfa AF: 0.311 Hom.: 913

Bravo AF: 0.318

Asia WGS AF: 0.273 AC: 943 AN: 3466

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	-0.90
Cadd	Benign	1.9
Dann	Benign	0.62

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: rs27970; hg19: chr5-102486723; COSMIC: COSV58603989; COSMIC: COSV58603989;