Variant rs146779637 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM4

The NM_021176.3(G6PC2):c.847C>T(p.Arg283Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00241 in 1,613,702 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0016 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0025 ( 9 hom. )

Consequence

G6PC2
NM_021176.3 stop_gained

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.278

Variant links:

Genes affected

G6PC2 (HGNC:28906): (glucose-6-phosphatase catalytic subunit 2) This gene encodes an enzyme belonging to the glucose-6-phosphatase catalytic subunit family. These enzymes are part of a multicomponent integral membrane system that catalyzes the hydrolysis of glucose-6-phosphate, the terminal step in gluconeogenic and glycogenolytic pathways, allowing the release of glucose into the bloodstream. The family member encoded by this gene is found in pancreatic islets and does not exhibit phosphohydrolase activity, but it is a major target of cell-mediated autoimmunity in diabetes. Several alternatively spliced transcript variants of this gene have been described, but their biological validity has not been determined. [provided by RefSeq, Jul 2008]

G6PC2 links:

SPC25 (HGNC:24031): (SPC25 component of NDC80 kinetochore complex) This gene encodes a protein that may be involved in kinetochore-microtubule interaction and spindle checkpoint activity. [provided by RefSeq, Jul 2008]

SPC25 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM4

Stoplost variant in NM_021176.3 Downstream stopcodon found after 368 codons.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
G6PC2	NM_021176.3 linkuse as main transcript	c.847C>T	p.Arg283Ter	stop_gained	5/5	ENST00000375363.8
G6PC2	XM_011511564.4 linkuse as main transcript	c.619C>T	p.Arg207Ter	stop_gained	3/3
G6PC2	XM_011511565.4 linkuse as main transcript	c.499C>T	p.Arg167Ter	stop_gained	4/4
G6PC2	NM_001081686.2 linkuse as main transcript	c.*266C>T		3_prime_UTR_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
G6PC2	ENST00000375363.8 linkuse as main transcript	c.847C>T	p.Arg283Ter	stop_gained	5/5	1	NM_021176.3	P1	Q9NQR9-1

Frequencies

GnomAD3 genomes

AF:

0.00158

AC:

240

AN:

152068

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000580

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000720

Gnomad ASJ

AF:

0.00433

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00276

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.00155

AC:

391

AN:

251478

Hom.:

AF XY:

0.00160

AC XY:

218

AN XY:

135912

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.000723

Gnomad ASJ exome

AF:

0.00377

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000719

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.00251

Gnomad OTH exome

AF:

0.00244

GnomAD4 exome

AF:

0.00249

AC:

3645

AN:

1461516

Hom.:

Cov.:

AF XY:

0.00240

AC XY:

1746

AN XY:

727102

show subpopulations

Gnomad4 AFR exome

AF:

0.000627

Gnomad4 AMR exome

AF:

0.000827

Gnomad4 ASJ exome

AF:

0.00394

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000638

Gnomad4 FIN exome

AF:

0.0000562

Gnomad4 NFE exome

AF:

0.00291

Gnomad4 OTH exome

AF:

0.00285

GnomAD4 genome

AF:

0.00158

AC:

240

AN:

152186

Hom.:

Cov.:

AF XY:

0.00132

AC XY:

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.000578

Gnomad4 AMR

AF:

0.000719

Gnomad4 ASJ

AF:

0.00433

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00276

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.00279

Hom.:

Bravo

AF:

0.00176

TwinsUK

AF:

0.00216

AC:

ALSPAC

AF:

0.00337

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00419

AC:

ExAC

AF:

0.00151

AC:

183

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00398

EpiControl

AF:

0.00273

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Fasting plasma glucose level quantitative trait locus 1

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genomic Research Center, Shahid Beheshti University of Medical Sciences

Mar 05, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.20

BayesDel_noAF

Pathogenic

0.51

Cadd

Pathogenic

Dann

Benign

0.97

Eigen

Benign

-0.089

Eigen_PC

Benign

-0.35

FATHMM_MKL

Benign

0.65

MutationTaster

Benign

1.0

Vest4

0.78

GERP RS

-0.72

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over