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

CA6831699

Gene: HNF1A

Condition: monogenic diabetes

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: f8d4c4d7-f7ec-4c7d-b06b-69fbc2db1e6b

HGVS expressions

NM_001306179.2:c.257T>A

NC_000012.12:g.120979025T>A

CM000674.2:g.120979025T>A

NC_000012.11:g.121416828T>A

CM000674.1:g.121416828T>A

NC_000012.10:g.119901211T>A

NG_011731.2:g.5280T>A

ENST00000257555.11:c.257T>A

ENST00000257555.10:c.257T>A

ENST00000400024.6:c.257T>A

ENST00000402929.5:n.392T>A

ENST00000535955.5:n.42+333T>A

ENST00000538626.2:n.190+185T>A

ENST00000538646.5:c.257T>A

ENST00000540108.1:c.257T>A

ENST00000541395.5:c.257T>A

ENST00000541924.5:c.257T>A

ENST00000543427.5:c.257T>A

ENST00000544413.2:c.257T>A

ENST00000544574.5:c.72+185T>A

ENST00000560968.5:n.400T>A

ENST00000615446.4:c.-258+314T>A

ENST00000617366.4:c.257T>A

NM_000545.5:c.257T>A

NM_000545.6:c.257T>A

NM_001306179.1:c.257T>A

NM_000545.8:c.257T>A

Uncertain Significance

PP3 BS1

PP4 PM1 BS2

Evidence Links 0

Expert Panel

Monogenic Diabetes VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Monogenic Diabetes VCEP

The c.257T>A variant in the HNF1 homeobox A gene, HNF1A, causes an amino acid change of leucine to histidine at codon 86 (p.(Leu86His)) of NM_000545.8. This variant is predicted to be deleterious by computational evidence, with a REVEL score of 0.8209, which is greater than or equal to the MDEP VCEP threshold of 0.70 (PP3). Also, this variant has a Popmax Filtering allele frequency in gnomAD 2.1.1 of 0.00004341, which is greater than or equal to the MDEP threshold for BS1 (≥0.000033) (BS1). In summary, c.257T>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 6/4/2021): PP3, BS1

PP3

REVEL 0.8209

BS1

Popmax Filtering AF 0.00004341 (> 0.000033)

PP4

MPC <50%

PM1

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

BS2

22 carriers in large biobank

Approved on: 2021-12-30

Published on: 2021-12-30

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