2-27497334-C-G

Variant names:

• chr2-27497334-C-G
• rs375836361
• NM_001486.4:c.151C>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001486.4(GCKR):​c.151C>G​(p.Arg51Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,862 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/19 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)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: GCKR NM_001486.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.542

Genes affected

GCKR (HGNC:4196): (glucokinase regulator) This gene encodes a protein belonging to the GCKR subfamily of the SIS (Sugar ISomerase) family of proteins. The gene product is a regulatory protein that inhibits glucokinase in liver and pancreatic islet cells by binding non-covalently to form an inactive complex with the enzyme. This gene is considered a susceptibility gene candidate for a form of maturity-onset diabetes of the young (MODY). [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30486482).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GCKR	NM_001486.4	c.151C>G	p.Arg51Gly	missense_variant	Exon 2 of 19	ENST00000264717.7	NP_001477.2
GCKR	XM_011532763.1	c.151C>G	p.Arg51Gly	missense_variant	Exon 2 of 13		XP_011531065.1
GCKR	XR_001738699.1	n.217C>G		non_coding_transcript_exon_variant	Exon 2 of 13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GCKR	ENST00000264717.7	c.151C>G	p.Arg51Gly	missense_variant	Exon 2 of 19	1	NM_001486.4	ENSP00000264717.2
GCKR	ENST00000472290.1	n.173C>G		non_coding_transcript_exon_variant	Exon 2 of 11	1
GCKR	ENST00000453813.1	c.67C>G	p.Arg23Gly	missense_variant	Exon 1 of 8	3		ENSP00000399463.1
GCKR	ENST00000417872.5	n.208C>G		non_coding_transcript_exon_variant	Exon 2 of 7	4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251488 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135918

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461862 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727238

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Uncertain	0.047	T
BayesDel_noAF	Uncertain	-0.070
CADD	Benign	15
DANN	Benign	0.95
DEOGEN2	Benign	0.38	T;T
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.89
FATHMM_MKL	Benign	0.035	N
LIST_S2	Benign	0.62	T;T
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.30	T;T
MetaSVM	Benign	-0.67	T
PrimateAI	Benign	0.20	T
PROVEAN	Uncertain	-4.2	D;D
REVEL	Uncertain	0.54
Sift	Benign	0.071	T;D
Sift4G	Benign	0.077	T;D
Vest4		0.71
MutPred		0.46		Loss of solvent accessibility (P = 0.0329);.;
MPC		0.071
ClinPred		0.60	D
GERP RS		-1.3
gMVP		0.37

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: rs375836361; hg19: chr2-27720201;