Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Link to SEPIO compliant JSON-LD document

Variant: NM_001354803.2:c.288-12_291del

CA2580610925

Gene: GCK

Condition: monogenic diabetes

Inheritance Mode: Semidominant inheritance

Link to MONDO

UUID: ea39e1e7-d40b-4a7c-b7a1-0247b408cbec

HGVS expressions

NM_001354803.2:c.288-12_291del

NC_000007.14:g.44145282_44145297del

CM000669.2:g.44145282_44145297del

NC_000007.13:g.44184881_44184896del

CM000669.1:g.44184881_44184896del

NC_000007.12:g.44151406_44151421del

NG_008847.1:g.49132_49147del

NG_008847.2:g.57879_57894del

ENST00000395796.8:c.*1252-12_*1255del

ENST00000616242.5:c.*374-12_*377del

ENST00000683378.1:n.480-12_483del

ENST00000336642.9:c.288-12_291del

ENST00000345378.7:c.1257-12_1260del

ENST00000403799.8:c.1254-12_1257del

ENST00000671824.1:c.1317-12_1320del

ENST00000672743.1:n.266-12_269del

ENST00000673284.1:c.1254-12_1257del

ENST00000336642.8:c.306-12_309del

ENST00000345378.6:c.1257-12_1260del

ENST00000395796.7:c.1251-12_1254del

ENST00000403799.7:c.1254-12_1257del

ENST00000437084.1:c.1203-12_1206del

ENST00000459642.1:n.634-12_637del

ENST00000616242.4:c.1251-12_1254del

NM_000162.3:c.1254-12_1257del

NM_033507.1:c.1257-12_1260del

NM_033508.1:c.1251-12_1254del

NM_000162.4:c.1254-12_1257del

NM_001354800.1:c.1254-12_1257del

NM_001354801.1:c.243-12_246del

NM_001354802.1:c.114-12_117del

NM_001354803.1:c.288-12_291del

NM_033507.2:c.1257-12_1260del

NM_033508.2:c.1251-12_1254del

NM_000162.5:c.1254-12_1257del

NM_033507.3:c.1257-12_1260del

NM_033508.3:c.1251-12_1254del

Pathogenic

PP4 PVS1 PM2_Supporting

Evidence Links 0

Expert Panel

Monogenic Diabetes VCEP

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.1254-12_1257del variant in the glucokinase gene, GCK, is predicted to remove a canonical splice acceptor site in intron 9 of NM_000162.5. This variant is predicted to cause skipping of biologically-relevant exon 10 of 10, not expected to lead to nonsense mediated decay but to result of the loss of a functionally important region of in a gene in which loss-of-function is an established disease mechanism (PVS1; PMID: 9790256). This variant was identified in an individual with a clinical history highly specific for GCK-MODY (FBG 5.5-8 mmol/L and HbA1c 5.6 - 7.6%) (internal lab contributors). This variant is absent from gnomAD v2.1.1 (PM2_Supporting). In summary, c.1254-12_1257del meets the criteria to be classified as pathogenic for monogenic diabetes. ACMG/AMP criteria applied, as specified by the ClinGen MDEP (specification version 1.3.0, approved 8/11/2023): PVS1, PP4, PM2_Supporting.

PP4

This variant was identified in an individual with a clinical history highly specific for GCK-MODY (FBG 5.5-8 mmol/L and HbA1c 5.6 - 7.6%) (internal lab contributors).

PVS1

This variant is predicted to cause skipping of biologically-relevant exon 10 of 10, not expected to lead to nonsense mediated decay but to result of the loss of a functionally important region of in a gene in which loss-of-function is an established disease mechanism (PVS1; PMID: 9790256).

PM2_Supporting

This variant is absent from gnomAD v2.1.1 (PM2_Supporting).

Approved on: 2023-09-20

Published on: 2023-09-20

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