rs560887

Positions:

• chr2-168906638-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.88

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]

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]

ACMG classification

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	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
G6PC2	NM_021176.3	c.441-26T>C		intron_variant		ENST00000375363.8	NP_066999.1
G6PC2	NM_001081686.2	c.441-930T>C		intron_variant			NP_001075155.1
G6PC2	XM_011511564.4	c.329-930T>C		intron_variant			XP_011509866.1
G6PC2	XM_011511565.4	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	c.441-26T>C		intron_variant		1	NM_021176.3	ENSP00000364512	P1

Frequencies

GnomAD3 genomes AF: 0.801 AC: 121709 AN: 152034 Hom.: 49694 Cov.: 31

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

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.: 13 AF XY: 0.751 AC XY: 379924 AN XY: 506166

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.: 31 AF XY: 0.804 AC XY: 59764 AN XY: 74340

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

Other links and lift over

dbSNP: rs560887; hg19: chr2-169763148;