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]

Variant: NM_001306179.2:c.1A>C

Curation Version - 1.1
Curation History
JSON LD for Version 1.1

CA386951959

1342948 (ClinVar)

Gene: HNF1A

Condition: monogenic diabetes

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 49ffa87c-44f9-4d04-bfeb-fc924bca0990

Approved on: 2022-03-04

Published on: 2022-07-11

HGVS expressions

NM_001306179.2:c.1A>C

NC_000012.12:g.120978769A>C

CM000674.2:g.120978769A>C

NC_000012.11:g.121416572A>C

CM000674.1:g.121416572A>C

NC_000012.10:g.119900955A>C

NG_011731.2:g.5024A>C

ENST00000257555.11:c.1A>C

ENST00000257555.10:c.1A>C

ENST00000400024.6:c.1A>C

ENST00000402929.5:n.136A>C

ENST00000535955.5:n.42+77A>C

ENST00000538626.2:n.119A>C

ENST00000538646.5:c.1A>C

ENST00000540108.1:c.1A>C

ENST00000541395.5:c.1A>C

ENST00000541924.5:c.1A>C

ENST00000543427.5:c.1A>C

ENST00000544413.2:c.1A>C

ENST00000544574.5:c.1A>C

ENST00000560968.5:n.144A>C

ENST00000615446.4:c.-258+58A>C

ENST00000617366.4:c.1A>C

NM_000545.5:c.1A>C

NM_000545.6:c.1A>C

NM_001306179.1:c.1A>C

NM_000545.8:c.1A>C

NM_000545.8(HNF1A):c.1A>C (p.Met1Leu)

Likely Pathogenic

The Expert Panel has overridden the computationally generated classification - "Uncertain Significance - Insufficient Evidence"

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 Version 1.1

PDF

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Monogenic Diabetes VCEP

The c.1A>C variant in the HNF1 homeobox A gene, HNF1A, results in the loss of the initiation codon (p.Met1?) of NM_000545.8. By altering the start codon of the coding sequence, this variant is predicted to cause a truncated or absent protein in a gene in which loss-of-function is an established disease mechanism (PVS1). This variant is absent from gnomAD v2.1.1 (PM2_Supporting). In summary, c.1A>C meets the criteria to be classified as likely pathogenic for monogenic diabetes. ACMG/AMP criteria applied, as specified by the ClinGen MDEP (specification version 1.1, approved 9/30/2021): PVS1, PM2_Supporting

PVS1

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

Curation History

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