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GeneBe

19-18169270-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_005027.4(PIK3R2):c.2163C>T(p.Pro721=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00619 in 1,518,744 control chromosomes in the GnomAD database, including 273 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. P721P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.010 ( 58 hom., cov: 33)
Exomes 𝑓: 0.0057 ( 215 hom. )

Consequence

PIK3R2
NM_005027.4 synonymous

Scores

1
1

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.47
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.36).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 19-18169270-C-T is Benign according to our data. Variant chr19-18169270-C-T is described in ClinVar as [Benign]. Clinvar id is 468322.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-1.47 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0584 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PIK3R2NM_005027.4 linkuse as main transcriptc.2163C>T p.Pro721= synonymous_variant 16/16 ENST00000222254.13
PIK3R2NR_073517.2 linkuse as main transcriptn.2767C>T non_coding_transcript_exon_variant 16/16
PIK3R2NR_162071.1 linkuse as main transcriptn.2505C>T non_coding_transcript_exon_variant 15/15

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PIK3R2ENST00000222254.13 linkuse as main transcriptc.2163C>T p.Pro721= synonymous_variant 16/161 NM_005027.4 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0102
AC:
1551
AN:
151834
Hom.:
56
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00143
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0612
Gnomad ASJ
AF:
0.00173
Gnomad EAS
AF:
0.0538
Gnomad SAS
AF:
0.0408
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000707
Gnomad OTH
AF:
0.0144
GnomAD3 exomes
AF:
0.0259
AC:
3092
AN:
119476
Hom.:
113
AF XY:
0.0250
AC XY:
1666
AN XY:
66642
show subpopulations
Gnomad AFR exome
AF:
0.00134
Gnomad AMR exome
AF:
0.0742
Gnomad ASJ exome
AF:
0.00220
Gnomad EAS exome
AF:
0.0617
Gnomad SAS exome
AF:
0.0399
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000839
Gnomad OTH exome
AF:
0.0131
GnomAD4 exome
AF:
0.00573
AC:
7834
AN:
1366802
Hom.:
215
Cov.:
32
AF XY:
0.00652
AC XY:
4402
AN XY:
674942
show subpopulations
Gnomad4 AFR exome
AF:
0.00126
Gnomad4 AMR exome
AF:
0.0695
Gnomad4 ASJ exome
AF:
0.00177
Gnomad4 EAS exome
AF:
0.0365
Gnomad4 SAS exome
AF:
0.0367
Gnomad4 FIN exome
AF:
0.0000295
Gnomad4 NFE exome
AF:
0.000770
Gnomad4 OTH exome
AF:
0.00918
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0103
AC:
1563
AN:
151942
Hom.:
58
Cov.:
33
AF XY:
0.0125
AC XY:
925
AN XY:
74274
show subpopulations
Gnomad4 AFR
AF:
0.00142
Gnomad4 AMR
AF:
0.0617
Gnomad4 ASJ
AF:
0.00173
Gnomad4 EAS
AF:
0.0538
Gnomad4 SAS
AF:
0.0406
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000707
Gnomad4 OTH
AF:
0.0166
Alfa
AF:
0.00148
Hom.:
0
Bravo
AF:
0.0131
Asia WGS
AF:
0.0500
AC:
173
AN:
3460

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1 Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJan 29, 2024- -
not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxSep 03, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.36
Cadd
Benign
0.87
Dann
Uncertain
0.98

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs147625988; hg19: chr19-18280080; API