12-18648027-G-C

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 2P and 8B. PM4BS1BS2

The NM_001288772.2(PIK3C2G):c.4460G>C(p.Ter1487Serext*?) variant causes a stop lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0157 in 1,581,494 control chromosomes in the GnomAD database, including 248 homozygotes. 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 0.012 ( 14 hom., cov: 32)

Exomes 𝑓: 0.016 ( 234 hom. )

Consequence

PIK3C2G
NM_001288772.2 stop_lost

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.72

Publications

8 publications found

Variant links:

Genes affected

PIK3C2G (HGNC:8973): (phosphatidylinositol-4-phosphate 3-kinase catalytic subunit type 2 gamma) The protein encoded by this gene belongs to the phosphoinositide 3-kinase (PI3K) family. PI3-kinases play roles in signaling pathways involved in cell proliferation, oncogenic transformation, cell survival, cell migration, and intracellular protein trafficking. This protein contains a lipid kinase catalytic domain as well as a C-terminal C2 domain, a characteristic of class II PI3-kinases. C2 domains act as calcium-dependent phospholipid binding motifs that mediate translocation of proteins to membranes, and may also mediate protein-protein interactions. This gene may play a role in several diseases, including type II diabetes. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]

PIK3C2G links:

PLCZ1 (HGNC:19218): (phospholipase C zeta 1) The protein encoded by this gene is a member of the phosphoinositide-specific phospholipase C family. Members in this family, classified into six isotypes that are tissue- and organ-specific, hydrolyze phosphatidylinositol 4,5-bisphosphate just before the phosphate group to yield diacylglycerol and inositol 1,4,5-trisphosphate. This protein localizes to the acrosome in spermatozoa and elicits Ca(2+) oscillations and egg activation during fertilization that leads to early embryonic development. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2012]

PLCZ1 Gene-Disease associations (from GenCC):

spermatogenic failure 17
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

PLCZ1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

PM4

Stoplost variant in NM_001288772.2 Downstream stopcodon found after 1532 codons.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0115 (1749/151858) while in subpopulation NFE AF = 0.0191 (1298/67956). AF 95% confidence interval is 0.0182. There are 14 homozygotes in GnomAd4. There are 794 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 14 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001288772.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PIK3C2G	NM_001288772.2	MANE Select	c.4460G>C	p.Ter1487Serext*?	stop_lost	Exon 33 of 33	NP_001275701.1	O75747-1
PIK3C2G	NM_004570.6		c.4337G>C	p.Ter1446Serext*?	stop_lost	Exon 32 of 32	NP_004561.3	O75747-2
PIK3C2G	NM_001288774.2		c.3794G>C	p.Ter1265Serext*?	stop_lost	Exon 33 of 33	NP_001275703.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PIK3C2G	ENST00000538779.6	TSL:5 MANE Select	c.4460G>C	p.Ter1487Serext*?	stop_lost	Exon 33 of 33	ENSP00000445381.1	O75747-1
PIK3C2G	ENST00000546003.5	TSL:1	n.*3757G>C		non_coding_transcript_exon	Exon 32 of 32	ENSP00000441618.1	F5GWG6
PIK3C2G	ENST00000546003.5	TSL:1	n.*3757G>C		3_prime_UTR	Exon 32 of 32	ENSP00000441618.1	F5GWG6

Frequencies

GnomAD3 genomes

AF:

0.0115

AC:

1751

AN:

151738

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00296

Gnomad AMI

AF:

0.0197

Gnomad AMR

AF:

0.00947

Gnomad ASJ

AF:

0.000578

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.00684

Gnomad FIN

AF:

0.0105

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0191

Gnomad OTH

AF:

0.0101

GnomAD2 exomes

AF:

0.0110

AC:

2503

AN:

227776

AF XY:

0.0117

show subpopulations

Gnomad AFR exome

AF:

0.00201

Gnomad AMR exome

AF:

0.00510

Gnomad ASJ exome

AF:

0.00161

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0108

Gnomad NFE exome

AF:

0.0174

Gnomad OTH exome

AF:

0.0110

GnomAD4 exome

AF:

0.0162

AC:

23134

AN:

1429636

Hom.:

234

Cov.:

AF XY:

0.0161

AC XY:

11450

AN XY:

710982

show subpopulations

African (AFR)

AF:

0.00232

AC:

AN:

32338

American (AMR)

AF:

0.00522

AC:

214

AN:

40988

Ashkenazi Jewish (ASJ)

AF:

0.00146

AC:

AN:

25352

East Asian (EAS)

AF:

0.00

AC:

AN:

38680

South Asian (SAS)

AF:

0.00774

AC:

628

AN:

81144

European-Finnish (FIN)

AF:

0.0108

AC:

570

AN:

52610

Middle Eastern (MID)

AF:

0.00302

AC:

AN:

5638

European-Non Finnish (NFE)

AF:

0.0190

AC:

20827

AN:

1093966

Other (OTH)

AF:

0.0130

AC:

766

AN:

58920

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

872

1744

2616

3488

4360

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

780

1560

2340

3120

3900

<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:

0.0115

AC:

1749

AN:

151858

Hom.:

Cov.:

AF XY:

0.0107

AC XY:

794

AN XY:

74208

show subpopulations

African (AFR)

AF:

0.00295

AC:

122

AN:

41344

American (AMR)

AF:

0.00946

AC:

144

AN:

15226

Ashkenazi Jewish (ASJ)

AF:

0.000578

AC:

AN:

3462

East Asian (EAS)

AF:

0.000387

AC:

AN:

5164

South Asian (SAS)

AF:

0.00643

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.0105

AC:

111

AN:

10574

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0191

AC:

1298

AN:

67956

Other (OTH)

AF:

0.00995

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

179

269

358

448

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:

0.0161

Hom.:

Bravo

AF:

0.0111

TwinsUK

AF:

0.0132

AC:

ALSPAC

AF:

0.0187

AC:

ESP6500AA

AF:

0.00190

AC:

ESP6500EA

AF:

0.0204

AC:

167

ExAC

AF:

0.0111

AC:

1335

Asia WGS

AF:

0.00375

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.45

CADD

Benign

(source)

DANN

Benign

0.77

Eigen

Pathogenic

0.81

Eigen_PC

Uncertain

0.59

FATHMM_MKL

Uncertain

0.86

PhyloP100

1.7

Vest4

0.015

GERP RS

3.2

Mutation Taster

=195/5

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over