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_001306179.2:c.47T>C

CA386952505

Gene: HNF1A

Condition: monogenic diabetes

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: c4db46ed-a169-478e-9da7-1d7d7bfe5e2e

Approved on: 2022-03-31

Published on: 2022-07-12

HGVS expressions

NM_001306179.2:c.47T>C

NC_000012.12:g.120978815T>C

CM000674.2:g.120978815T>C

NC_000012.11:g.121416618T>C

CM000674.1:g.121416618T>C

NC_000012.10:g.119901001T>C

NG_011731.2:g.5070T>C

ENST00000257555.11:c.47T>C

ENST00000257555.10:c.47T>C

ENST00000400024.6:c.47T>C

ENST00000402929.5:n.182T>C

ENST00000535955.5:n.42+123T>C

ENST00000538626.2:n.165T>C

ENST00000538646.5:c.47T>C

ENST00000540108.1:c.47T>C

ENST00000541395.5:c.47T>C

ENST00000541924.5:c.47T>C

ENST00000543427.5:c.47T>C

ENST00000544413.2:c.47T>C

ENST00000544574.5:c.47T>C

ENST00000560968.5:n.190T>C

ENST00000615446.4:c.-258+104T>C

ENST00000617366.4:c.47T>C

NM_000545.5:c.47T>C

NM_000545.6:c.47T>C

NM_001306179.1:c.47T>C

NM_000545.8:c.47T>C

Uncertain Significance

PM1_Supporting PP3 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 Version 1.1

PDF

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Monogenic Diabetes VCEP

The c.47T>C variant in the HNF1 homeobox A gene, HNF1A, causes an amino acid change of leucine to proline at codon 16 (p.(Leu16Pro)) of NM_000545.8. This variant is located within the DNA dimerization domain (codons 1-32) of HNF1A, which is defined as critical for the protein’s function by the ClinGen MDEP (PM1_Supporting). This variant is absent from gnomAD v2.1.1 (PM2_Supporting). Additionally, this variant is predicted to be deleterious by computational evidence, with a REVEL score of 0.937, which is greater than the MDEP VCEP threshold of 0.70 (PP3). In summary, c.47T>C meets the criteria to be classified as a variant of uncertain significance for monogenic diabetes. ACMG/AMP criteria applied, as specified by the ClinGen MDEP (specification version 1.1, approved 9/30/21): PM1_Supporting, PM2_Supporting, PP3.

PM1_Supporting

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

PP3

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

PM2_Supporting

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

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