rs2072513

Variant names:

• chr22-20745009-T-C
• rs2072513
• NM_058004.4:c.3364-289A>G

Your query was ambiguous. Multiple possible variants found:

• chr22-20745009-T-C
• chr22-20745009-T-A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_058004.4(PI4KA):​c.3364-289A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.41 in 152,016 control chromosomes in the GnomAD database, including 13,235 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.41 (13235 hom., cov: 31)
• Consequence: PI4KA NM_058004.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.610
• Publications: 15 publications found

Genes affected

PI4KA (HGNC:8983): (phosphatidylinositol 4-kinase alpha) This gene encodes a phosphatidylinositol (PI) 4-kinase which catalyzes the first committed step in the biosynthesis of phosphatidylinositol 4,5-bisphosphate. The mammalian PI 4-kinases have been classified into two types, II and III, based on their molecular mass, and modulation by detergent and adenosine. The protein encoded by this gene is a type III enzyme that is not inhibited by adenosine. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Apr 2018]

PI4KA Gene-Disease associations (from GenCC):

• polymicrogyria, perisylvian, with cerebellar hypoplasia and arthrogryposis

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 22-20745009-T-C is Benign according to our data. Variant chr22-20745009-T-C is described in ClinVar as Benign. ClinVar VariationId is 1231695.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.486 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_058004.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PI4KA	NM_058004.4	MANE Select	c.3364-289A>G		intron	N/A	NP_477352.3	P42356-1
	PI4KA	NM_001362863.2		c.3298-289A>G		intron	N/A	NP_001349792.1
	PI4KA	NM_001362862.2		c.3364-2245A>G		intron	N/A	NP_001349791.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PI4KA	ENST00000255882.11	TSL:1 MANE Select	c.3364-289A>G		intron	N/A	ENSP00000255882.6	P42356-1
	PI4KA	ENST00000939414.1		c.3364-289A>G		intron	N/A	ENSP00000609473.1
	PI4KA	ENST00000939412.1		c.3364-289A>G		intron	N/A	ENSP00000609471.1

Frequencies

GnomAD3 genomes AF: 0.410 AC: 62261 AN: 151898 Hom.: 13214 Cov.: 31

Gnomad AFR AF: 0.492

Gnomad AMI AF: 0.510

Gnomad AMR AF: 0.470

Gnomad ASJ AF: 0.454

Gnomad EAS AF: 0.452

Gnomad SAS AF: 0.337

Gnomad FIN AF: 0.229

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.372

Gnomad OTH AF: 0.442

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

GnomAD4 genome AF: 0.410 AC: 62322 AN: 152016 Hom.: 13235 Cov.: 31 AF XY: 0.404 AC XY: 30020 AN XY: 74282

African (AFR) AF: 0.492 AC: 20377 AN: 41434

American (AMR) AF: 0.471 AC: 7189 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.454 AC: 1575 AN: 3468

East Asian (EAS) AF: 0.452 AC: 2335 AN: 5164

South Asian (SAS) AF: 0.336 AC: 1623 AN: 4824

European-Finnish (FIN) AF: 0.229 AC: 2418 AN: 10570

Middle Eastern (MID) AF: 0.469 AC: 137 AN: 292

European-Non Finnish (NFE) AF: 0.372 AC: 25274 AN: 67982

Other (OTH) AF: 0.441 AC: 930 AN: 2110

Alfa AF: 0.363 Hom.: 6342

Bravo AF: 0.436

Asia WGS AF: 0.412 AC: 1431 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.9
DANN	Benign	0.36
PhyloP100		-0.61
Mutation Taster		=100/0	polymorphism (auto)

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: rs2072513; hg19: chr22-21099297;