Variant chr2-168906638-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_021176.3(G6PC2):c.441-26T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.755 in 1,126,534 control chromosomes in the GnomAD database, including 326,000 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 0.80 ( 49757 hom., cov: 31)

Exomes 𝑓: 0.75 ( 276243 hom. )

Consequence

G6PC2
NM_021176.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.88

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.944 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
G6PC2	NM_021176.3 linkuse as main transcript	c.441-26T>C	intron_variant	ENST00000375363.8	NP_066999.1
G6PC2	NM_001081686.2 linkuse as main transcript	c.441-930T>C	intron_variant		NP_001075155.1
G6PC2	XM_011511564.4 linkuse as main transcript	c.329-930T>C	intron_variant		XP_011509866.1
G6PC2	XM_011511565.4 linkuse as main transcript	c.93-26T>C	intron_variant		XP_011509867.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
G6PC2	ENST00000375363.8 linkuse as main transcript	c.441-26T>C		intron_variant		1	NM_021176.3	ENSP00000364512	P1	Q9NQR9-1

Frequencies

GnomAD3 genomes

AF:

0.801

AC:

121709

AN:

152034

Hom.:

49694

Cov.:

show subpopulations

Gnomad AFR

AF:

0.947

Gnomad AMI

AF:

0.780

Gnomad AMR

AF:

0.812

Gnomad ASJ

AF:

0.793

Gnomad EAS

AF:

0.966

Gnomad SAS

AF:

0.885

Gnomad FIN

AF:

0.708

Gnomad MID

AF:

0.763

Gnomad NFE

AF:

0.705

Gnomad OTH

AF:

0.794

GnomAD3 exomes

AF:

0.790

AC:

198206

AN:

250980

Hom.:

79660

AF XY:

0.784

AC XY:

106450

AN XY:

135692

show subpopulations

Gnomad AFR exome

AF:

0.951

Gnomad AMR exome

AF:

0.876

Gnomad ASJ exome

AF:

0.805

Gnomad EAS exome

AF:

0.967

Gnomad SAS exome

AF:

0.875

Gnomad FIN exome

AF:

0.702

Gnomad NFE exome

AF:

0.705

Gnomad OTH exome

AF:

0.756

GnomAD4 exome

AF:

0.748

AC:

728381

AN:

974384

Hom.:

276243

Cov.:

AF XY:

0.751

AC XY:

379924

AN XY:

506166

show subpopulations

Gnomad4 AFR exome

AF:

0.953

Gnomad4 AMR exome

AF:

0.870

Gnomad4 ASJ exome

AF:

0.813

Gnomad4 EAS exome

AF:

0.971

Gnomad4 SAS exome

AF:

0.872

Gnomad4 FIN exome

AF:

0.698

Gnomad4 NFE exome

AF:

0.705

Gnomad4 OTH exome

AF:

0.767

GnomAD4 genome

AF:

0.801

AC:

121832

AN:

152150

Hom.:

49757

Cov.:

AF XY:

0.804

AC XY:

59764

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.948

Gnomad4 AMR

AF:

0.813

Gnomad4 ASJ

AF:

0.793

Gnomad4 EAS

AF:

0.966

Gnomad4 SAS

AF:

0.885

Gnomad4 FIN

AF:

0.708

Gnomad4 NFE

AF:

0.705

Gnomad4 OTH

AF:

0.794

Alfa

AF:

0.732

Hom.:

84882

Bravo

AF:

0.816

Asia WGS

AF:

0.916

AC:

3185

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

0.18

DANN

Benign

0.74

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over