10-22537249-T-C

Variant names:

• chr10-22537249-T-C
• rs80142698
• NM_005028.5:c.1173A>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_005028.5(PIP4K2A):​c.1173A>G​(p.Glu391Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00312 in 1,606,956 control chromosomes in the GnomAD database, including 117 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.016 (49 hom., cov: 32)
  • Exomes 𝑓: 0.0018 (68 hom.)
• Consequence: PIP4K2A NM_005028.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.86
• Publications: 3 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP6: Variant 10-22537249-T-C is Benign according to our data. Variant chr10-22537249-T-C is described in ClinVar as [Benign]. Clinvar id is 779110.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.86 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0508 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIP4K2A	NM_005028.5	c.1173A>G	p.Glu391Glu	synonymous_variant	Exon 10 of 10	ENST00000376573.9	NP_005019.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIP4K2A	ENST00000376573.9	c.1173A>G	p.Glu391Glu	synonymous_variant	Exon 10 of 10	1	NM_005028.5	ENSP00000365757.4
PIP4K2A	ENST00000545335.5	c.996A>G	p.Glu332Glu	synonymous_variant	Exon 10 of 10	2		ENSP00000442098.1
PIP4K2A	ENST00000323883.11	c.753A>G	p.Glu251Glu	synonymous_variant	Exon 8 of 8	2		ENSP00000326294.7
PIP4K2A	ENST00000474335.1	n.203A>G		non_coding_transcript_exon_variant	Exon 2 of 2	2

Frequencies

GnomAD3 genomes AF: 0.0155 AC: 2362 AN: 152134 Hom.: 49 Cov.: 32

Gnomad AFR AF: 0.0526

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00811

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000367

Gnomad OTH AF: 0.0139

GnomAD2 exomes AF: 0.00420 AC: 1008 AN: 239906 AF XY: 0.00297

Gnomad AFR exome AF: 0.0534

Gnomad AMR exome AF: 0.00386

Gnomad ASJ exome AF: 0.00144

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000316

Gnomad OTH exome AF: 0.00388

GnomAD4 exome AF: 0.00182 AC: 2647 AN: 1454704 Hom.: 68 Cov.: 31 AF XY: 0.00160 AC XY: 1153 AN XY: 722866

African (AFR) AF: 0.0547 AC: 1822 AN: 33292

American (AMR) AF: 0.00513 AC: 227 AN: 44256

Ashkenazi Jewish (ASJ) AF: 0.00170 AC: 44 AN: 25882

East Asian (EAS) AF: 0.00 AC: 0 AN: 39582

South Asian (SAS) AF: 0.000188 AC: 16 AN: 84948

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53046

Middle Eastern (MID) AF: 0.00608 AC: 35 AN: 5758

European-Non Finnish (NFE) AF: 0.000212 AC: 235 AN: 1107816

Other (OTH) AF: 0.00446 AC: 268 AN: 60124

GnomAD4 genome AF: 0.0156 AC: 2370 AN: 152252 Hom.: 49 Cov.: 32 AF XY: 0.0148 AC XY: 1104 AN XY: 74456

African (AFR) AF: 0.0527 AC: 2187 AN: 41512

American (AMR) AF: 0.00810 AC: 124 AN: 15302

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10620

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

European-Non Finnish (NFE) AF: 0.000368 AC: 25 AN: 68022

Other (OTH) AF: 0.0137 AC: 29 AN: 2114

Alfa AF: 0.00754 Hom.: 15

Bravo AF: 0.0174

Asia WGS AF: 0.00491 AC: 17 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Oct 09, 2017

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	7.1
DANN	Benign	0.50
PhyloP100		1.9
Mutation Taster		=88/12	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: rs80142698; hg19: chr10-22826178;