10-22541928-G-A

Variant names:

• chr10-22541928-G-A
• rs62640376
• NM_005028.5:c.912C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_005028.5(PIP4K2A):​c.912C>T​(p.Ser304Ser) 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
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 2259 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIP4K2A	NM_005028.5	c.912C>T	p.Ser304Ser	synonymous_variant	Exon 8 of 10	ENST00000376573.9	NP_005019.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIP4K2A	ENST00000376573.9	c.912C>T	p.Ser304Ser	synonymous_variant	Exon 8 of 10	1	NM_005028.5	ENSP00000365757.4
PIP4K2A	ENST00000545335.5	c.735C>T	p.Ser245Ser	synonymous_variant	Exon 8 of 10	2		ENSP00000442098.1
PIP4K2A	ENST00000323883.11	c.492C>T	p.Ser164Ser	synonymous_variant	Exon 6 of 8	2		ENSP00000326294.7
PIP4K2A	ENST00000604912.1	c.*24C>T		downstream_gene_variant		2		ENSP00000473858.1

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

GnomAD2 exomes AF: 0.00396 AC: 995 AN: 251310 AF XY: 0.00276

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 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

African (AFR) AF: 0.0513 AC: 1717 AN: 33474

American (AMR) AF: 0.00389 AC: 174 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00168 AC: 44 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000151 AC: 13 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00347 AC: 20 AN: 5768

European-Non Finnish (NFE) AF: 0.000146 AC: 162 AN: 1111950

Other (OTH) AF: 0.00396 AC: 239 AN: 60396

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

African (AFR) AF: 0.0506 AC: 2100 AN: 41504

American (AMR) AF: 0.00739 AC: 113 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00115 AC: 4 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.0000944 AC: 1 AN: 10594

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000206 AC: 14 AN: 68002

Other (OTH) AF: 0.0128 AC: 27 AN: 2112

Alfa AF: 0.00801 Hom.: 12

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

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Oct 09, 2017

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	6.1
DANN	Benign	0.66
PhyloP100		-0.15
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

dbSNP: rs62640376; hg19: chr10-22830857;