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

CA6831851

Gene: HNF1A

Condition: monogenic diabetes

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: bc8899de-cf3c-40cb-abd0-39b2047217d8

HGVS expressions

NM_001306179.2:c.866C>A

NC_000012.12:g.120994316C>A

CM000674.2:g.120994316C>A

NC_000012.11:g.121432119C>A

CM000674.1:g.121432119C>A

NC_000012.10:g.119916502C>A

NG_011731.2:g.20571C>A

ENST00000257555.11:c.866C>A

ENST00000257555.10:c.866C>A

ENST00000400024.6:c.866C>A

ENST00000402929.5:n.1001C>A

ENST00000535955.5:n.43-3175C>A

ENST00000538626.2:n.191-3175C>A

ENST00000538646.5:c.679C>A

ENST00000540108.1:c.*306C>A

ENST00000541395.5:c.866C>A

ENST00000541924.5:c.713+610C>A

ENST00000543427.5:c.633+690C>A

ENST00000544413.2:c.866C>A

ENST00000544574.5:c.73-2301C>A

ENST00000560968.5:n.893+116C>A

ENST00000615446.4:c.-257-1946C>A

ENST00000617366.4:c.586+737C>A

NM_000545.5:c.866C>A

NM_000545.6:c.866C>A

NM_001306179.1:c.866C>A

NM_000545.8:c.866C>A

Uncertain Significance

PM2_Supporting

PP4 PM5

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.866C>A variant in the e.g. HNF1 homeobox A gene, HNF1A, causes an amino acid change of proline to histidine at codon 289 (p.(Pro289His)) of NM_000545.8. This variant is also absent from gnomAD v2.1.1 (PM2_Supporting). This variant was identified in an individual with diabetes; however, the MODY probability is unable to be calculated due to lack of treatment information, and therefore, PP4 will not be applied (internal lab contributors). Two other missense variants, c.865C>T (p.Pro289Ser) and c.866C>G (p.Pro289Arg), have been classified as VUS by the ClinGen MDEP; therefore, PM5 will not be applied. In summary, c.866C>A 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): PM2_Supporting.

PM2_Supporting

Absent from gnomAD v2.1.1 ENF and 1 copy in SAS.

PP4

This variant was identified in an individual with diabetes; however, the MODY probability is unable to be calculated due to lack of treatment information (internal lab contributors).

PM5

Two other missense variants, c.865C>T (p.Pro289Ser) and c.866C>G (p.Pro289Arg), have been classified as VUS by the ClinGen MDEP; therefore, PM5 will not be applied.

Approved on: 2022-04-15

Published on: 2022-07-12

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