19-18156170-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_005027.4(PIK3R2):c.291C>T(p.Pro97Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00131 in 1,451,484 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0071 ( 15 hom., cov: 33)

Exomes 𝑓: 0.00063 ( 7 hom. )

Consequence

PIK3R2
NM_005027.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -5.36

Publications

0 publications found

Variant links:

Genes affected

PIK3R2 (HGNC:8980): (phosphoinositide-3-kinase regulatory subunit 2) Phosphatidylinositol 3-kinase (PI3K) is a lipid kinase that phosphorylates phosphatidylinositol and similar compounds, creating second messengers important in growth signaling pathways. PI3K functions as a heterodimer of a regulatory and a catalytic subunit. The protein encoded by this gene is a regulatory component of PI3K. Three transcript variants, one protein coding and the other two non-protein coding, have been found for this gene. [provided by RefSeq, Apr 2019]

PIK3R2 Gene-Disease associations (from GenCC):

megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Illumina, G2P, Genomics England PanelApp
overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
megalencephaly-polymicrogyria-postaxial polydactyly-hydrocephalus syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

PIK3R2 links:

ENSG00000268173 (HGNC:):

ENSG00000268173 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.65).

BP6

Variant 19-18156170-C-T is Benign according to our data. Variant chr19-18156170-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 468324.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-5.36 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00707 (1077/152326) while in subpopulation AFR AF = 0.0251 (1043/41572). AF 95% confidence interval is 0.0238. There are 15 homozygotes in GnomAd4. There are 497 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High AC in GnomAd4 at 1077 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIK3R2	NM_005027.4 link	c.291C>T	p.Pro97Pro	synonymous_variant	Exon 2 of 16	ENST00000222254.13	NP_005018.2	O00459
PIK3R2	NR_073517.2 link	n.846C>T		non_coding_transcript_exon_variant	Exon 2 of 16
PIK3R2	NR_162071.1 link	n.846C>T		non_coding_transcript_exon_variant	Exon 2 of 15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIK3R2	ENST00000222254.13 link	c.291C>T	p.Pro97Pro	synonymous_variant	Exon 2 of 16	1	NM_005027.4	ENSP00000222254.6		O00459
ENSG00000268173	ENST00000593731.1 link	n.291C>T		non_coding_transcript_exon_variant	Exon 2 of 25	2		ENSP00000471914.1

Frequencies

GnomAD3 genomes

AF:

0.00708

AC:

1078

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0252

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00137

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:

0.0000294

Gnomad OTH

AF:

0.00525

GnomAD2 exomes

AF:

0.00168

AC:

122

AN:

72606

AF XY:

0.00133

show subpopulations

Gnomad AFR exome

AF:

0.0291

Gnomad AMR exome

AF:

0.00158

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000113

Gnomad OTH exome

AF:

0.00128

GnomAD4 exome

AF:

0.000631

AC:

820

AN:

1299158

Hom.:

Cov.:

AF XY:

0.000550

AC XY:

349

AN XY:

634070

show subpopulations

African (AFR)

AF:

0.0258

AC:

659

AN:

25520

American (AMR)

AF:

0.00183

AC:

AN:

18626

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18100

East Asian (EAS)

AF:

0.00

AC:

AN:

32074

South Asian (SAS)

AF:

0.000128

AC:

AN:

62584

European-Finnish (FIN)

AF:

0.00

AC:

AN:

45022

Middle Eastern (MID)

AF:

0.00123

AC:

AN:

4896

European-Non Finnish (NFE)

AF:

0.0000192

AC:

AN:

1039136

Other (OTH)

AF:

0.00175

AC:

AN:

53200

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

143

190

238

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

<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:

0.00707

AC:

1077

AN:

152326

Hom.:

Cov.:

AF XY:

0.00667

AC XY:

497

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.0251

AC:

1043

AN:

41572

American (AMR)

AF:

0.00137

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68022

Other (OTH)

AF:

0.00520

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

109

164

218

273

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00527

Hom.:

Bravo

AF:

0.00810

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Oct 19, 2021

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1

Benign:1

Jan 20, 2025

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

-0.65

CADD

Benign

0.74

(source)

DANN

Benign

0.88

PhyloP100

-5.4

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over