rs2242375

Variant names:

• chr17-8803133-T-A
• rs2242375
• NM_001010855.4:c.*140A>T

Your query was ambiguous. Multiple possible variants found:

• chr17-8803133-T-A
• chr17-8803133-T-C
• chr17-8803133-T-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000619866.5(PIK3R6):​c.*140A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PIK3R6 ENST00000619866.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.291
• Publications: 0 publications found

Genes affected

PIK3R6 (HGNC:27101): (phosphoinositide-3-kinase regulatory subunit 6) Phosphoinositide 3-kinase gamma is a lipid kinase that produces the lipid second messenger phosphatidylinositol 3,4,5-trisphosphate. The kinase is composed of a catalytic subunit and one of several regulatory subunits, and is chiefly activated by G protein-coupled receptors. This gene encodes a regulatory subunit, and is distantly related to the phosphoinositide-3-kinase, regulatory subunit 5 gene which is located adjacent to this gene on chromosome 7. The orthologous protein in the mouse binds to both the catalytic subunit and to G(beta/gamma), and mediates activation of the kinase subunit downstream of G protein-coupled receptors. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2014]

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000619866.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIK3R6	NM_001010855.4	MANE Select	c.*140A>T		3_prime_UTR	Exon 20 of 20	NP_001010855.1
	PIK3R6	NR_110865.1		n.2881A>T		non_coding_transcript_exon	Exon 20 of 20
	PIK3R6	NM_001290211.1		c.*140A>T		3_prime_UTR	Exon 20 of 20	NP_001277140.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIK3R6	ENST00000619866.5	TSL:5 MANE Select	c.*140A>T		3_prime_UTR	Exon 20 of 20	ENSP00000480157.1
	PIK3R6	ENST00000611951.4	TSL:2	n.*2470A>T		non_coding_transcript_exon	Exon 20 of 20	ENSP00000480685.1
	PIK3R6	ENST00000613555.4	TSL:2	n.*2338A>T		non_coding_transcript_exon	Exon 20 of 20	ENSP00000484155.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 967326 Hom.: 0 Cov.: 13 AF XY: 0.00 AC XY: 0 AN XY: 486550

African (AFR) AF: 0.00 AC: 0 AN: 22210

American (AMR) AF: 0.00 AC: 0 AN: 25356

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17528

East Asian (EAS) AF: 0.00 AC: 0 AN: 34946

South Asian (SAS) AF: 0.00 AC: 0 AN: 60532

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43970

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2944

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 716690

Other (OTH) AF: 0.00 AC: 0 AN: 43150

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	1.8
DANN	Benign	0.84
PhyloP100		0.29

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: rs2242375; hg19: chr17-8706451;