dbSNP rs146779637: G6PC2:p.Arg283* (chr2-168907858-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_021176.3(G6PC2):c.847C>T(p.Arg283*) 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, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 0.278

Publications

19 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High Homozygotes in GnomAdExome4 at 9 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
G6PC2	NM_021176.3 link	c.847C>T	p.Arg283*	stop_gained	Exon 5 of 5	ENST00000375363.8	NP_066999.1	Q9NQR9-1
G6PC2	XM_011511564.4 link	c.619C>T	p.Arg207*	stop_gained	Exon 3 of 3		XP_011509866.1
G6PC2	XM_011511565.4 link	c.499C>T	p.Arg167*	stop_gained	Exon 4 of 4		XP_011509867.1
G6PC2	NM_001081686.2 link	c.*266C>T		3_prime_UTR_variant	Exon 4 of 4		NP_001075155.1	Q9NQR9-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
G6PC2	ENST00000375363.8 link	c.847C>T	p.Arg283*	stop_gained	Exon 5 of 5	1	NM_021176.3	ENSP00000364512.3		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

GnomAD2 exomes

AF:

0.00155

AC:

391

AN:

251478

AF XY:

0.00160

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 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

African (AFR)

AF:

0.000627

AC:

AN:

33470

American (AMR)

AF:

0.000827

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00394

AC:

103

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.000638

AC:

AN:

86248

European-Finnish (FIN)

AF:

0.0000562

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00295

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00291

AC:

3237

AN:

1111676

Other (OTH)

AF:

0.00285

AC:

172

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

214

428

643

857

1071

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00158

AC:

240

AN:

152186

Hom.:

Cov.:

AF XY:

0.00132

AC XY:

AN XY:

74402

show subpopulations

African (AFR)

AF:

0.000578

AC:

AN:

41520

American (AMR)

AF:

0.000719

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00433

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.000208

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00276

AC:

188

AN:

68008

Other (OTH)

AF:

0.000474

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00246

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:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Fasting plasma glucose level quantitative trait locus 1

Uncertain:1

Mar 05, 2018

Genomic Research Center, Shahid Beheshti University of Medical Sciences

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.20

BayesDel_noAF

Pathogenic

0.51

CADD

Pathogenic

(source)

DANN

Benign

0.97

Eigen

Benign

-0.089

Eigen_PC

Benign

-0.35

FATHMM_MKL

Benign

0.65

PhyloP100

0.28

Vest4

0.78

GERP RS

-0.72

Mutation Taster

=81/119

disease causing

(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

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rs146779637

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over