rs2232316

Variant names:

• chr2-168901052-G-A
• rs2232316
• ENST00000451987.5:c.-172-10366C>T

Your query was ambiguous. Multiple possible variants found:

• chr2-168901052-G-A
• chr2-168901052-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000451987.5(SPC25):​c.-172-10366C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 152,210 control chromosomes in the GnomAD database, including 919 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 0.11 (919 hom., cov: 33)
• Consequence: SPC25 ENST00000451987.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.06
• Publications: 20 publications found

Genes affected

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]

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.137 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
G6PC2	NM_021176.3	c.-280G>A		upstream_gene_variant		ENST00000375363.8	NP_066999.1
G6PC2	NM_001081686.2	c.-280G>A		upstream_gene_variant			NP_001075155.1
G6PC2	XM_011511564.4	c.-280G>A		upstream_gene_variant			XP_011509866.1
G6PC2	XM_011511565.4	c.-518G>A		upstream_gene_variant			XP_011509867.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
G6PC2	ENST00000375363.8	c.-280G>A		upstream_gene_variant		1	NM_021176.3	ENSP00000364512.3

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16705 AN: 152092 Hom.: 920 Cov.: 33

Gnomad AFR AF: 0.133

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.141

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.116

Gnomad SAS AF: 0.0533

Gnomad FIN AF: 0.0576

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.101

Gnomad OTH AF: 0.124

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.110 AC: 16734 AN: 152210 Hom.: 919 Cov.: 33 AF XY: 0.107 AC XY: 7939 AN XY: 74424

African (AFR) AF: 0.133 AC: 5533 AN: 41516

American (AMR) AF: 0.142 AC: 2165 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.115 AC: 398 AN: 3470

East Asian (EAS) AF: 0.116 AC: 602 AN: 5184

South Asian (SAS) AF: 0.0539 AC: 260 AN: 4822

European-Finnish (FIN) AF: 0.0576 AC: 610 AN: 10598

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.101 AC: 6836 AN: 68014

Other (OTH) AF: 0.125 AC: 263 AN: 2110

Alfa AF: 0.106 Hom.: 1003

Bravo AF: 0.123

Asia WGS AF: 0.103 AC: 359 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	14
DANN	Benign	0.55
PhyloP100		2.1
PromoterAI		0.020	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2232316; hg19: chr2-169757562;