2-27497406-AAG-AAGAG

Variant names:

• chr2-27497406-A-AAG
• NM_001486.4:c.216+9_216+10dupGA

Variant summary

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

The ENST00000264717.7(GCKR):​c.216+7_216+8insAG variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GCKR ENST00000264717.7 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.60

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GCKR	NM_001486.4	c.216+9_216+10dupGA		intron_variant	Intron 2 of 18	ENST00000264717.7	NP_001477.2
GCKR	XM_011532763.1	c.216+9_216+10dupGA		intron_variant	Intron 2 of 12		XP_011531065.1
GCKR	XR_001738699.1	n.282+9_282+10dupGA		intron_variant	Intron 2 of 12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GCKR	ENST00000264717.7	c.216+7_216+8insAG		splice_region_variant, intron_variant	Intron 2 of 18	1	NM_001486.4	ENSP00000264717.2
GCKR	ENST00000472290.1	n.238+7_238+8insAG		splice_region_variant, intron_variant	Intron 2 of 10	1
GCKR	ENST00000453813.1	c.132+7_132+8insAG		splice_region_variant, intron_variant	Intron 1 of 7	3		ENSP00000399463.1
GCKR	ENST00000417872.5	n.273+7_273+8insAG		splice_region_variant, intron_variant	Intron 2 of 6	4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-27720273;