chr10-22541928-G-A

Position:

• chr10-22541928-G-A

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_005028.5(PIP4K2A):​c.912C>T​(p.Ser304=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00287 in 1,613,992 control chromosomes in the GnomAD database, including 99 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.015 (43 hom., cov: 32)
  • Exomes 𝑓: 0.0016 (56 hom.)
• Consequence: PIP4K2A NM_005028.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.153

Genes affected

PIP4K2A (HGNC:8997): (phosphatidylinositol-5-phosphate 4-kinase type 2 alpha) Phosphatidylinositol-5,4-bisphosphate, the precursor to second messengers of the phosphoinositide signal transduction pathways, is thought to be involved in the regulation of secretion, cell proliferation, differentiation, and motility. The protein encoded by this gene is one of a family of enzymes capable of catalyzing the phosphorylation of phosphatidylinositol-5-phosphate on the fourth hydroxyl of the myo-inositol ring to form phosphatidylinositol-5,4-bisphosphate. The amino acid sequence of this enzyme does not show homology to other kinases, but the recombinant protein does exhibit kinase activity. This gene is a member of the phosphatidylinositol-5-phosphate 4-kinase family. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP6: Variant 10-22541928-G-A is Benign according to our data. Variant chr10-22541928-G-A is described in ClinVar as [Benign]. Clinvar id is 779111.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.153 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0148 (2259/152180) while in subpopulation AFR AF= 0.0506 (2100/41504). AF 95% confidence interval is 0.0488. There are 43 homozygotes in gnomad4. There are 1058 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 2259 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIP4K2A	NM_005028.5	c.912C>T	p.Ser304=	synonymous_variant	8/10	ENST00000376573.9	NP_005019.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIP4K2A	ENST00000376573.9	c.912C>T	p.Ser304=	synonymous_variant	8/10	1	NM_005028.5	ENSP00000365757	P1
PIP4K2A	ENST00000545335.5	c.735C>T	p.Ser245=	synonymous_variant	8/10	2		ENSP00000442098
PIP4K2A	ENST00000323883.11	c.492C>T	p.Ser164=	synonymous_variant	6/8	2		ENSP00000326294
PIP4K2A	ENST00000604912.1			downstream_gene_variant		2		ENSP00000473858

Frequencies

GnomAD3 genomes AF: 0.0148 AC: 2252 AN: 152062 Hom.: 43 Cov.: 32

Gnomad AFR AF: 0.0506

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00740

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000944

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.0129

GnomAD3 exomes AF: 0.00396 AC: 995 AN: 251310 Hom.: 22 AF XY: 0.00276 AC XY: 375 AN XY: 135812

Gnomad AFR exome AF: 0.0514

Gnomad AMR exome AF: 0.00281

Gnomad ASJ exome AF: 0.00149

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000196

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000229

Gnomad OTH exome AF: 0.00261

GnomAD4 exome AF: 0.00162 AC: 2369 AN: 1461812 Hom.: 56 Cov.: 33 AF XY: 0.00139 AC XY: 1008 AN XY: 727228

Gnomad4 AFR exome AF: 0.0513

Gnomad4 AMR exome AF: 0.00389

Gnomad4 ASJ exome AF: 0.00168

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000151

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000146

Gnomad4 OTH exome AF: 0.00396

GnomAD4 genome AF: 0.0148 AC: 2259 AN: 152180 Hom.: 43 Cov.: 32 AF XY: 0.0142 AC XY: 1058 AN XY: 74406

Gnomad4 AFR AF: 0.0506

Gnomad4 AMR AF: 0.00739

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0000944

Gnomad4 NFE AF: 0.000206

Gnomad4 OTH AF: 0.0128

Alfa AF: 0.00748 Hom.: 11

Bravo AF: 0.0165

Asia WGS AF: 0.00462 AC: 16 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Oct 09, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	6.1
DANN	Benign	0.66
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs62640376; hg19: chr10-22830857;