2-27497406-AAG-A

Variant names:

• chr2-27497406-AAG-A
• rs57332022
• NM_001486.4:c.216+9_216+10delGA

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The ENST00000264717.7(GCKR):​c.216+8_216+9delAG variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00702 in 1,614,048 control chromosomes in the GnomAD database, including 711 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.037 (323 hom., cov: 32)
  • Exomes 𝑓: 0.0039 (388 hom.)
• Consequence: GCKR ENST00000264717.7 splice_region, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• 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

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant 2-27497406-AAG-A is Benign according to our data. Variant chr2-27497406-AAG-A is described in ClinVar as [Benign]. Clinvar id is 1334327.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.125 is higher than 0.05.

Transcripts

RefSeq

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

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GCKR	ENST00000264717.7	c.216+8_216+9delAG		splice_region_variant, intron_variant	Intron 2 of 18	1	NM_001486.4	ENSP00000264717.2
GCKR	ENST00000472290.1	n.238+8_238+9delAG		splice_region_variant, intron_variant	Intron 2 of 10	1
GCKR	ENST00000453813.1	c.132+8_132+9delAG		splice_region_variant, intron_variant	Intron 1 of 7	3		ENSP00000399463.1
GCKR	ENST00000417872.5	n.273+8_273+9delAG		splice_region_variant, intron_variant	Intron 2 of 6	4

Frequencies

GnomAD3 genomes AF: 0.0368 AC: 5596 AN: 152136 Hom.: 319 Cov.: 32

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0147

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000397

Gnomad OTH AF: 0.0263

GnomAD2 exomes AF: 0.00948 AC: 2383 AN: 251422 AF XY: 0.00703

Gnomad AFR exome AF: 0.132

Gnomad AMR exome AF: 0.00538

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000193

Gnomad OTH exome AF: 0.00408

GnomAD4 exome AF: 0.00390 AC: 5696 AN: 1461794 Hom.: 388 AF XY: 0.00337 AC XY: 2449 AN XY: 727216

Gnomad4 AFR exome AF: 0.141 AC: 4720 AN: 33462

Gnomad4 AMR exome AF: 0.00626 AC: 280 AN: 44724

Gnomad4 ASJ exome AF: 0.00 AC: 0 AN: 26136

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 39700

Gnomad4 SAS exome AF: 0.000464 AC: 40 AN: 86252

Gnomad4 FIN exome AF: 0.00 AC: 0 AN: 53412

Gnomad4 NFE exome AF: 0.0000917 AC: 102 AN: 1111946

Gnomad4 Remaining exome AF: 0.00838 AC: 506 AN: 60394

GnomAD4 genome AF: 0.0370 AC: 5627 AN: 152254 Hom.: 323 Cov.: 32 AF XY: 0.0365 AC XY: 2716 AN XY: 74458

Gnomad4 AFR AF: 0.128 AC: 0.128041 AN: 0.128041

Gnomad4 AMR AF: 0.0146 AC: 0.0146405 AN: 0.0146405

Gnomad4 ASJ AF: 0.00 AC: 0 AN: 0

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.000414 AC: 0.000414422 AN: 0.000414422

Gnomad4 FIN AF: 0.00 AC: 0 AN: 0

Gnomad4 NFE AF: 0.000397 AC: 0.000396907 AN: 0.000396907

Gnomad4 OTH AF: 0.0260 AC: 0.0260417 AN: 0.0260417

Alfa AF: 0.0194 Hom.: 26

Bravo AF: 0.0425

Asia WGS AF: 0.0110 AC: 40 AN: 3478

EpiCase AF: 0.000218

EpiControl AF: 0.000296

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jan 22, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 15, 2022

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Mutation Taster		=100/0	polymorphism (auto)

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: rs57332022; hg19: chr2-27720273;