chr2-27497372-G-C

Variant names:

• chr2-27497372-G-C
• rs34775423
• NM_001486.4:c.189G>C

Variant summary

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

The NM_001486.4(GCKR):​c.189G>C​(p.Glu63Asp) 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. 12/19 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)
• Consequence: GCKR NM_001486.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.61

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23244485).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GCKR	NM_001486.4	c.189G>C	p.Glu63Asp	missense_variant	Exon 2 of 19	ENST00000264717.7	NP_001477.2
GCKR	XM_011532763.1	c.189G>C	p.Glu63Asp	missense_variant	Exon 2 of 13		XP_011531065.1
GCKR	XR_001738699.1	n.255G>C		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.189G>C	p.Glu63Asp	missense_variant	Exon 2 of 19	1	NM_001486.4	ENSP00000264717.2
GCKR	ENST00000472290.1	n.211G>C		non_coding_transcript_exon_variant	Exon 2 of 11	1
GCKR	ENST00000453813.1	c.105G>C	p.Glu35Asp	missense_variant	Exon 1 of 8	3		ENSP00000399463.1
GCKR	ENST00000417872.5	n.246G>C		non_coding_transcript_exon_variant	Exon 2 of 7	4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Uncertain	0.044	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.25	T;T
Eigen	Benign	-0.056
Eigen_PC	Benign	0.070
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.76	T;T
M_CAP	Benign	0.044	D
MetaRNN	Benign	0.23	T;T
MetaSVM	Uncertain	-0.26	T
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.74	N;N
REVEL	Uncertain	0.33
Sift	Benign	0.11	T;T
Sift4G	Benign	0.087	T;T
Vest4		0.29
MutPred		0.37		Gain of helix (P = 0.132);.;
MVP		0.81
MPC		0.14
ClinPred		0.53	D
GERP RS		3.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.46

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: rs34775423; hg19: chr2-27720239;