2-168906638-T-C

Variant names:

• chr2-168906638-T-C
• rs560887
• NM_021176.3:c.441-26T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 257 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021176.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	G6PC2	NM_021176.3	MANE Select	c.441-26T>C		intron	N/A	NP_066999.1	Q9NQR9-1
	G6PC2	NM_001081686.2		c.441-930T>C		intron	N/A	NP_001075155.1	Q9NQR9-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	G6PC2	ENST00000375363.8	TSL:1 MANE Select	c.441-26T>C		intron	N/A	ENSP00000364512.3	Q9NQR9-1
	G6PC2	ENST00000282075.5	TSL:1	n.*22-26T>C		intron	N/A	ENSP00000282075.4	Q9NQR9-2
	G6PC2	ENST00000461586.1	TSL:1	n.157-930T>C		intron	N/A

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

GnomAD2 exomes AF: 0.790 AC: 198206 AN: 250980 AF XY: 0.784

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 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

African (AFR) AF: 0.953 AC: 23215 AN: 24370

American (AMR) AF: 0.870 AC: 38403 AN: 44118

Ashkenazi Jewish (ASJ) AF: 0.813 AC: 18819 AN: 23146

East Asian (EAS) AF: 0.971 AC: 36462 AN: 37542

South Asian (SAS) AF: 0.872 AC: 66721 AN: 76508

European-Finnish (FIN) AF: 0.698 AC: 36933 AN: 52920

Middle Eastern (MID) AF: 0.760 AC: 3698 AN: 4864

European-Non Finnish (NFE) AF: 0.705 AC: 470117 AN: 666576

Other (OTH) AF: 0.767 AC: 34013 AN: 44340

GnomAD4 genome AF: 0.801 AC: 121832 AN: 152150 Hom.: 49757 Cov.: 31 AF XY: 0.804 AC XY: 59764 AN XY: 74340

African (AFR) AF: 0.948 AC: 39355 AN: 41534

American (AMR) AF: 0.813 AC: 12421 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.793 AC: 2755 AN: 3472

East Asian (EAS) AF: 0.966 AC: 4999 AN: 5174

South Asian (SAS) AF: 0.885 AC: 4271 AN: 4824

European-Finnish (FIN) AF: 0.708 AC: 7482 AN: 10562

Middle Eastern (MID) AF: 0.772 AC: 227 AN: 294

European-Non Finnish (NFE) AF: 0.705 AC: 47932 AN: 67978

Other (OTH) AF: 0.794 AC: 1679 AN: 2114

Alfa AF: 0.741 Hom.: 191060

Bravo AF: 0.816

Asia WGS AF: 0.916 AC: 3185 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.18
DANN	Benign	0.74
PhyloP100		-1.9
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs560887; hg19: chr2-169763148;