2-27497495-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001486.4(GCKR):c.217-67C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00141 in 1,565,922 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0076 (11 hom., cov: 32)
  • Exomes 𝑓: 0.00074 (8 hom.)
• Consequence: GCKR NM_001486.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.431

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 2-27497495-C-G is Benign according to our data. Variant chr2-27497495-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 1218676.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00762 (1161/152298) while in subpopulation AFR AF= 0.0263 (1094/41552). AF 95% confidence interval is 0.025. There are 11 homozygotes in gnomad4. There are 521 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GCKR	NM_001486.4	c.217-67C>G		intron_variant		ENST00000264717.7
GCKR	XM_011532763.1	c.217-67C>G		intron_variant
GCKR	XR_001738699.1	n.283-67C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GCKR	ENST00000264717.7	c.217-67C>G		intron_variant		1	NM_001486.4	P1
GCKR	ENST00000472290.1	n.239-67C>G		intron_variant, non_coding_transcript_variant		1
GCKR	ENST00000453813.1	c.133-67C>G		intron_variant		3
GCKR	ENST00000417872.5	n.274-67C>G		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.00763 AC: 1161 AN: 152178 Hom.: 11 Cov.: 32

Gnomad AFR AF: 0.0264

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00295

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.00478

GnomAD4 exome AF: 0.000738 AC: 1043 AN: 1413624 Hom.: 8 Cov.: 24 AF XY: 0.000636 AC XY: 449 AN XY: 706322

Gnomad4 AFR exome AF: 0.0261

Gnomad4 AMR exome AF: 0.00132

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000586

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000421

Gnomad4 OTH exome AF: 0.00143

GnomAD4 genome AF: 0.00762 AC: 1161 AN: 152298 Hom.: 11 Cov.: 32 AF XY: 0.00700 AC XY: 521 AN XY: 74468

Gnomad4 AFR AF: 0.0263

Gnomad4 AMR AF: 0.00294

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000162

Gnomad4 OTH AF: 0.00473

Alfa AF: 0.00600 Hom.: 1

Bravo AF: 0.00834

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 25, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	6.0
Dann	Benign	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: rs113580320; hg19: chr2-27720362;