Genetic Variant ENSG00000293427:n.697G>A (chr22-21483071-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The ENST00000462560.6(ENSG00000293427):n.697G>A variant causes a non coding transcript exon change involving the alteration of a conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000030 ( 0 hom., cov: 16)

Exomes 𝑓: 0.000017 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ENSG00000293427
ENST00000462560.6 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.35

Publications

2 publications found

Variant links:

Genes affected

ENSG00000293427 (HGNC:):

ENSG00000293427 links:

PI4KAP2 (HGNC:33577): (phosphatidylinositol 4-kinase alpha pseudogene 2) Predicted to enable 1-phosphatidylinositol 4-kinase activity. Predicted to be involved in phosphatidylinositol phosphate biosynthetic process and phosphatidylinositol-mediated signaling. Predicted to be active in cytoplasm and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

PI4KAP2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.3).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PI4KAP2	NR_003700.1 link	n.964G>A		non_coding_transcript_exon_variant	Exon 8 of 17

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
ENSG00000293427	ENST00000462560.6 link	n.697G>A	non_coding_transcript_exon_variant	Exon 6 of 15	1
ENSG00000293427	ENST00000479693.1 link	n.993G>A	non_coding_transcript_exon_variant	Exon 8 of 13	1
PI4KAP2	ENST00000360806.9 link	n.673G>A	non_coding_transcript_exon_variant	Exon 6 of 16	6

Frequencies

GnomAD3 genomes

AF:

0.0000297

AC:

AN:

134606

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000257

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000489

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000188

AC:

AN:

159696

AF XY:

0.0000237

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000324

Gnomad OTH exome

AF:

0.000224

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000174

AC:

AN:

1321968

Hom.:

Cov.:

AF XY:

0.0000168

AC XY:

AN XY:

654310

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

31576

American (AMR)

AF:

0.00

AC:

AN:

34590

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24464

East Asian (EAS)

AF:

0.00

AC:

AN:

32492

South Asian (SAS)

AF:

0.0000256

AC:

AN:

78238

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47386

Middle Eastern (MID)

AF:

0.000197

AC:

AN:

5082

European-Non Finnish (NFE)

AF:

0.0000148

AC:

AN:

1013500

Other (OTH)

AF:

0.0000915

AC:

AN:

54640

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000000000000888178), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.310

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000297

AC:

AN:

134606

Hom.:

Cov.:

AF XY:

0.0000154

AC XY:

AN XY:

64748

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0000257

AC:

AN:

38924

American (AMR)

AF:

0.00

AC:

AN:

11724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3248

East Asian (EAS)

AF:

0.00

AC:

AN:

3866

South Asian (SAS)

AF:

0.00

AC:

AN:

3714

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8894

Middle Eastern (MID)

AF:

0.00

AC:

AN:

306

European-Non Finnish (NFE)

AF:

0.0000489

AC:

AN:

61290

Other (OTH)

AF:

0.00

AC:

AN:

1786

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.0332287), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.400

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000480

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.30

CADD

Benign

(source)

DANN

Benign

0.90

PhyloP100

7.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over