2-168908046-G-C

Variant names:

• chr2-168908046-G-C
• rs993287550
• NM_021176.3:c.1035G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_021176.3(G6PC2):​c.1035G>C​(p.Met345Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: G6PC2 NM_021176.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.147

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07488561).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
G6PC2	NM_021176.3	c.1035G>C	p.Met345Ile	missense_variant	Exon 5 of 5	ENST00000375363.8	NP_066999.1
G6PC2	XM_011511564.4	c.807G>C	p.Met269Ile	missense_variant	Exon 3 of 3		XP_011509866.1
G6PC2	XM_011511565.4	c.687G>C	p.Met229Ile	missense_variant	Exon 4 of 4		XP_011509867.1
G6PC2	NM_001081686.2	c.*454G>C		3_prime_UTR_variant	Exon 4 of 4		NP_001075155.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
G6PC2	ENST00000375363.8	c.1035G>C	p.Met345Ile	missense_variant	Exon 5 of 5	1	NM_021176.3	ENSP00000364512.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	3.3
DANN	Benign	0.65
DEOGEN2	Benign	0.19	T
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.55
FATHMM_MKL	Benign	0.51	D
LIST_S2	Benign	0.32	T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.075	T
MetaSVM	Benign	-0.80	T
MutationAssessor	Benign	1.4	L
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.81	N
REVEL	Benign	0.17
Sift	Benign	0.43	T
Sift4G	Benign	0.46	T
Polyphen		0.0	B
Vest4		0.11
MutPred		0.32		Loss of MoRF binding (P = 0.0733);
MVP		0.53
MPC		0.032
ClinPred		0.096	T
GERP RS		4.0
Varity_R		0.084
gMVP		0.16

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: rs993287550; hg19: chr2-169764556;