Variant 2-168907638-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6BP7BS2

The NM_021176.3(G6PC2):c.627G>A(p.Lys209Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00216 in 1,613,948 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0016 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0022 ( 8 hom. )

Consequence

G6PC2
NM_021176.3 synonymous

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.07

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.44).

BP6

Variant 2-168907638-G-A is Benign according to our data. Variant chr2-168907638-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3041171.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=2.07 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 8 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
G6PC2	NM_021176.3 link	c.627G>A	p.Lys209Lys	synonymous_variant	Exon 5 of 5	ENST00000375363.8	NP_066999.1	Q9NQR9-1
G6PC2	XM_011511564.4 link	c.399G>A	p.Lys133Lys	synonymous_variant	Exon 3 of 3		XP_011509866.1
G6PC2	XM_011511565.4 link	c.279G>A	p.Lys93Lys	synonymous_variant	Exon 4 of 4		XP_011509867.1
G6PC2	NM_001081686.2 link	c.*46G>A		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.627G>A	p.Lys209Lys	synonymous_variant	Exon 5 of 5	1	NM_021176.3	ENSP00000364512.3		Q9NQR9-1

Frequencies

GnomAD3 genomes

AF:

0.00156

AC:

237

AN:

152138

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000507

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00249

Gnomad ASJ

AF:

0.000577

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000623

Gnomad FIN

AF:

0.000848

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00229

Gnomad OTH

AF:

0.00383

GnomAD3 exomes

AF:

0.00138

AC:

348

AN:

251446

Hom.:

AF XY:

0.00141

AC XY:

191

AN XY:

135894

show subpopulations

Gnomad AFR exome

AF:

0.000554

Gnomad AMR exome

AF:

0.000694

Gnomad ASJ exome

AF:

0.00159

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000621

Gnomad FIN exome

AF:

0.000647

Gnomad NFE exome

AF:

0.00225

Gnomad OTH exome

AF:

0.00163

GnomAD4 exome

AF:

0.00222

AC:

3245

AN:

1461692

Hom.:

Cov.:

AF XY:

0.00217

AC XY:

1576

AN XY:

727178

show subpopulations

Gnomad4 AFR exome

AF:

0.000448

Gnomad4 AMR exome

AF:

0.00123

Gnomad4 ASJ exome

AF:

0.00115

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000464

Gnomad4 FIN exome

AF:

0.00101

Gnomad4 NFE exome

AF:

0.00262

Gnomad4 OTH exome

AF:

0.00220

GnomAD4 genome

AF:

0.00156

AC:

237

AN:

152256

Hom.:

Cov.:

AF XY:

0.00165

AC XY:

123

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.000505

Gnomad4 AMR

AF:

0.00248

Gnomad4 ASJ

AF:

0.000577

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000623

Gnomad4 FIN

AF:

0.000848

Gnomad4 NFE

AF:

0.00229

Gnomad4 OTH

AF:

0.00379

Alfa

AF:

0.00233

Hom.:

Bravo

AF:

0.00195

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

G6PC2-related disorder

Benign:1

Apr 01, 2019

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Benign

0.58

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.16

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