Variant 2-27497406-AAG-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_001486.4(GCKR):c.216+9_216+10del 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
NM_001486.4 splice_region, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.60

Variant links:

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]

GCKR links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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	Effect	MANE	Protein
GCKR	NM_001486.4 linkuse as main transcript	c.216+9_216+10del	splice_region_variant, intron_variant	ENST00000264717.7	NP_001477.2
GCKR	XM_011532763.1 linkuse as main transcript	c.216+9_216+10del	splice_region_variant, intron_variant		XP_011531065.1
GCKR	XR_001738699.1 linkuse as main transcript	n.282+9_282+10del	splice_region_variant, intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris
GCKR	ENST00000264717.7 linkuse as main transcript	c.216+9_216+10del	splice_region_variant, intron_variant	1	NM_001486.4	ENSP00000264717	P1
GCKR	ENST00000472290.1 linkuse as main transcript	n.238+9_238+10del	splice_region_variant, intron_variant, non_coding_transcript_variant	1
GCKR	ENST00000453813.1 linkuse as main transcript	c.132+9_132+10del	splice_region_variant, intron_variant	3		ENSP00000399463
GCKR	ENST00000417872.5 linkuse as main transcript	n.273+9_273+10del	splice_region_variant, intron_variant, non_coding_transcript_variant	4

Frequencies

GnomAD3 genomes

AF:

0.0368

AC:

5596

AN:

152136

Hom.:

319

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.00948

AC:

2383

AN:

251422

Hom.:

153

AF XY:

0.00703

AC XY:

956

AN XY:

135902

show subpopulations

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 SAS exome

AF:

0.000392

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

show subpopulations

Gnomad4 AFR exome

AF:

0.141

Gnomad4 AMR exome

AF:

0.00626

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000917

Gnomad4 OTH exome

AF:

0.00838

GnomAD4 genome

AF:

0.0370

AC:

5627

AN:

152254

Hom.:

323

Cov.:

AF XY:

0.0365

AC XY:

2716

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.128

Gnomad4 AMR

AF:

0.0146

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000397

Gnomad4 OTH

AF:

0.0260

Alfa

AF:

0.0194

Hom.:

Bravo

AF:

0.0425

Asia WGS

AF:

0.0110

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.000296

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 15, 2022	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over