chr2-27496919-A-ACGGTTT
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PM4
The NM_001486.4(GCKR):c.17_22dup(p.Arg6_Phe7dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0002 in 1,613,826 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Genomes: 𝑓 0.00015 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00020 ( 0 hom. )
Consequence
GCKR
NM_001486.4 inframe_insertion
NM_001486.4 inframe_insertion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -1.26
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PM4
Nonframeshift variant in NON repetitive region in NM_001486.4.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| GCKR | NM_001486.4 | c.17_22dup | p.Arg6_Phe7dup | inframe_insertion | 1/19 | ENST00000264717.7 | NP_001477.2 | |
| GCKR | XM_011532763.1 | c.17_22dup | p.Arg6_Phe7dup | inframe_insertion | 1/13 | XP_011531065.1 | ||
| GCKR | XR_001738699.1 | n.83_88dup | non_coding_transcript_exon_variant | 1/13 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| GCKR | ENST00000264717.7 | c.17_22dup | p.Arg6_Phe7dup | inframe_insertion | 1/19 | 1 | NM_001486.4 | ENSP00000264717 | P1 | |
| GCKR | ENST00000472290.1 | n.39_44dup | non_coding_transcript_exon_variant | 1/11 | 1 | |||||
| GCKR | ENST00000417872.5 | n.74_79dup | non_coding_transcript_exon_variant | 1/7 | 4 |
Frequencies
GnomAD3 genomes 0.000151 AC: 23AN: 152108Hom.: 0 Cov.: 32
GnomAD3 genomes
AF:
AC:
23
AN:
152108
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.000167 AC: 42AN: 251462Hom.: 0 AF XY: 0.000191 AC XY: 26AN XY: 135906
GnomAD3 exomes
AF:
AC:
42
AN:
251462
Hom.:
AF XY:
AC XY:
26
AN XY:
135906
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.000205 AC: 299AN: 1461600Hom.: 0 Cov.: 30 AF XY: 0.000204 AC XY: 148AN XY: 727144
GnomAD4 exome
AF:
AC:
299
AN:
1461600
Hom.:
Cov.:
30
AF XY:
AC XY:
148
AN XY:
727144
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome 0.000151 AC: 23AN: 152226Hom.: 0 Cov.: 32 AF XY: 0.000175 AC XY: 13AN XY: 74426
GnomAD4 genome
AF:
AC:
23
AN:
152226
Hom.:
Cov.:
32
AF XY:
AC XY:
13
AN XY:
74426
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Uncertain:3
| Uncertain significance, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
| Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Aug 12, 2024 | Identified in a patient with hypertriglyceridemia, reported as p.Q8_H9insRF due to the use of alternate nomenclature; however, specific clinical information was not provided (PMID: 20657596); In-frame insertion of 2 amino acids in a non-repeat region; One in vitro functional study suggests that this variant has a mild impact on protein function and does not affect protein expression (PMID: 24879641); This variant is associated with the following publications: (PMID: 20657596, 34426522, 24879641, 36325899) - |
| Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Nov 14, 2023 | This variant, c.17_22dup, results in the insertion of 2 amino acid(s) of the GCKR protein (p.Arg6_Phe7dup), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs748731892, gnomAD 0.02%). This variant has been observed in individual(s) with hypertriglyceridemia (PMID: 20657596). ClinVar contains an entry for this variant (Variation ID: 1303199). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies have shown that this variant does not substantially affect GCKR function (PMID: 24879641). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Fasting plasma glucose level quantitative trait locus 5 Uncertain:1
| Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 02, 2021 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at