rs760900069

Variant names:

• chr19-18155875-C-T
• rs760900069
• NM_005027.4:c.-5C>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The NM_005027.4(PIK3R2):​c.-5C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000189 in 1,537,846 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000019 (0 hom.)
• Consequence: PIK3R2 NM_005027.4 5_prime_UTR
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -2.64
• Publications: 0 publications found

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: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Illumina, G2P
• 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

ENSG00000268173 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 19-18155875-C-T is Benign according to our data. Variant chr19-18155875-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3045637.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High AC in GnomAdExome4 at 26 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005027.4. 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
	PIK3R2	NM_005027.4	MANE Select	c.-5C>T		5_prime_UTR	Exon 2 of 16	NP_005018.2	O00459
	PIK3R2	NR_073517.2		n.551C>T		non_coding_transcript_exon	Exon 2 of 16
	PIK3R2	NR_162071.1		n.551C>T		non_coding_transcript_exon	Exon 2 of 15

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIK3R2	ENST00000222254.13	TSL:1 MANE Select	c.-5C>T		5_prime_UTR	Exon 2 of 16	ENSP00000222254.6	O00459
	ENSG00000268173	ENST00000593731.1	TSL:2	n.-5C>T		non_coding_transcript_exon	Exon 2 of 25	ENSP00000471914.1
	PIK3R2	ENST00000617130.6	TSL:1	n.-5C>T		non_coding_transcript_exon	Exon 2 of 15	ENSP00000477864.2	A0A7I2U3A3

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152220 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

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: 0.00

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000493 AC: 7 AN: 141850 AF XY: 0.0000524

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000194

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000559

Gnomad OTH exome AF: 0.000247

GnomAD4 exome AF: 0.0000188 AC: 26 AN: 1385626 Hom.: 0 Cov.: 31 AF XY: 0.0000190 AC XY: 13 AN XY: 682702

African (AFR) AF: 0.00 AC: 0 AN: 30276

American (AMR) AF: 0.00 AC: 0 AN: 34068

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24418

East Asian (EAS) AF: 0.00 AC: 0 AN: 35082

South Asian (SAS) AF: 0.0000128 AC: 1 AN: 78016

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47786

Middle Eastern (MID) AF: 0.000177 AC: 1 AN: 5634

European-Non Finnish (NFE) AF: 0.0000205 AC: 22 AN: 1073000

Other (OTH) AF: 0.0000349 AC: 2 AN: 57346

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152220 Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3 AN XY: 74366

African (AFR) AF: 0.0000241 AC: 1 AN: 41458

American (AMR) AF: 0.0000654 AC: 1 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68030

Other (OTH) AF: 0.000478 AC: 1 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000227

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	PIK3R2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.1
DANN	Benign	0.94
PhyloP100		-2.6
Mutation Taster		=300/0	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: rs760900069; hg19: chr19-18266685;