5-103129219-G-C

Position:

• chr5-103129219-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.-284-87G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.244 in 153,482 control chromosomes in the GnomAD database, including 5,230 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.24 (5172 hom., cov: 32)
  • Exomes 𝑓: 0.25 (58 hom.)
• Consequence: PPIP5K2 NM_001276277.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.319

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=-0.87).
• BP6: Variant 5-103129219-G-C is Benign according to our data. Variant chr5-103129219-G-C is described in ClinVar as [Benign]. Clinvar id is 1273990.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.433 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPIP5K2	NM_001276277.3	c.-284-87G>C		intron_variant		ENST00000358359.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPIP5K2	ENST00000358359.8	c.-284-87G>C		intron_variant		1	NM_001276277.3	P4

Frequencies

GnomAD3 genomes AF: 0.244 AC: 37119 AN: 151924 Hom.: 5171 Cov.: 32

Gnomad AFR AF: 0.121

Gnomad AMI AF: 0.429

Gnomad AMR AF: 0.231

Gnomad ASJ AF: 0.225

Gnomad EAS AF: 0.448

Gnomad SAS AF: 0.141

Gnomad FIN AF: 0.324

Gnomad MID AF: 0.207

Gnomad NFE AF: 0.300

Gnomad OTH AF: 0.242

GnomAD4 exome AF: 0.253 AC: 364 AN: 1440 Hom.: 58 AF XY: 0.253 AC XY: 192 AN XY: 758

Gnomad4 AFR exome AF: 0.161

Gnomad4 AMR exome AF: 0.108

Gnomad4 ASJ exome AF: 0.227

Gnomad4 EAS exome AF: 0.402

Gnomad4 SAS exome AF: 0.125

Gnomad4 FIN exome AF: 0.313

Gnomad4 NFE exome AF: 0.264

Gnomad4 OTH exome AF: 0.192

GnomAD4 genome AF: 0.244 AC: 37147 AN: 152042 Hom.: 5172 Cov.: 32 AF XY: 0.244 AC XY: 18124 AN XY: 74340

Gnomad4 AFR AF: 0.122

Gnomad4 AMR AF: 0.231

Gnomad4 ASJ AF: 0.225

Gnomad4 EAS AF: 0.448

Gnomad4 SAS AF: 0.141

Gnomad4 FIN AF: 0.324

Gnomad4 NFE AF: 0.300

Gnomad4 OTH AF: 0.241

Alfa AF: 0.273 Hom.: 762

Bravo AF: 0.234

Asia WGS AF: 0.258 AC: 892 AN: 3474

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	-0.87
CADD	Benign	3.4
DANN	Benign	0.54

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: rs26525; hg19: chr5-102464923; COSMIC: COSV58603925; COSMIC: COSV58603925;