The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
  • No ClinVar Id was directly found from the curated document


Variant: NM_001354803.2:c.402del

CA2017997779

Gene: GCK
Condition: monogenic diabetes
Inheritance Mode: Semidominant inheritance
UUID: 8c1172cd-9ba7-4c5e-8711-2c33aa4ac895

HGVS expressions

NM_001354803.2:c.402del
NC_000007.14:g.44145167del
CM000669.2:g.44145167del
NC_000007.13:g.44184766del
CM000669.1:g.44184766del
NC_000007.12:g.44151291del
NG_008847.1:g.49258del
NG_008847.2:g.58005del
ENST00000395796.8:c.*1366del
ENST00000616242.5:c.*488del
ENST00000683378.1:n.594del
ENST00000336642.9:c.402del
ENST00000345378.7:c.1371del
ENST00000403799.8:c.1368del
ENST00000671824.1:c.1431del
ENST00000672743.1:n.380del
ENST00000673284.1:c.1368del
ENST00000336642.8:n.420del
ENST00000345378.6:c.1371del
ENST00000395796.7:c.1365del
ENST00000403799.7:c.1368del
ENST00000437084.1:c.1317del
ENST00000459642.1:n.748del
ENST00000616242.4:n.1365del
NM_000162.3:c.1368del
NM_033507.1:c.1371del
NM_033508.1:c.1365del
NM_000162.4:c.1368del
NM_001354800.1:c.1368del
NM_001354801.1:c.357del
NM_001354802.1:c.228del
NM_001354803.1:c.402del
NM_033507.2:c.1371del
NM_033508.2:c.1365del
NM_000162.5:c.1368del
NM_033507.3:c.1371del
NM_033508.3:c.1365del

Likely Pathogenic

Met criteria codes 2
PVS1 PM2_Supporting
Not Met criteria codes 2
PS4 PP4

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specification: ClinGen Monogenic Diabetes Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for GCK Version 1.2.0

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
Monogenic Diabetes VCEP
The c.1368del variant in the glucokinase gene, GCK, causes a frameshift in the protein at codon 457 (NM_000545.6), adding 157 novel amino acids before encountering a stop codon (p.(Cys457Valfs157)). This variant, located in exon 10 of 10, is predicted to cause loss of a stop codon and result in an elongated protein. The additional residues are expected to cause improper folding, resulting in loss of function in a gene in which loss-of-function is an established disease mechanism (PVS1; PMID 19790256). This variant is absent from gnomAD 2.1.1 (PM2_Supporting). In summary, c.1368del meets the criteria to be classified as likely pathogenic for monogenic diabetes. ACMG/AMP criteria applied, as specified by the ClinGen MDEP (specification version 1.2.0, approved 6/7/2023): PVS1, PM2_Supporting.
Met criteria codes
PVS1
This variant, located in exon 10 of 10, is predicted to cause loss of a stop codon and result in an elongated protein. The additional residues are expected to cause improper folding, resulting in loss of function in a gene in which loss-of-function is an established disease mechanism (PVS1; PMID 19790256).
PM2_Supporting
Absent in gnomAD
Not Met criteria codes
PS4
One case by internal lab contributor, no clinical information provided
PP4
No case-level information provided
Approved on: 2023-06-19
Published on: 2023-06-19
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