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_000545.6(HNF1A):c.801_802insGGG (p.Phe268_Ala269insGly)

CA658658179

447502 (ClinVar)

Gene: HNF1A

Condition: monogenic diabetes

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 4068d35c-0f31-4f22-a500-ee217fb31046

HGVS expressions

NM_000545.6:c.801_802insGGG

NM_000545.6(HNF1A):c.801_802insGGG (p.Phe268_Ala269insGly)

NC_000012.12:g.120994251_120994252insGGG

CM000674.2:g.120994251_120994252insGGG

NC_000012.11:g.121432054_121432055insGGG

CM000674.1:g.121432054_121432055insGGG

NC_000012.10:g.119916437_119916438insGGG

NG_011731.2:g.20506_20507insGGG

ENST00000257555.11:c.801_802insGGG

ENST00000257555.10:c.801_802insGGG

ENST00000400024.6:c.801_802insGGG

ENST00000402929.5:n.936_937insGGG

ENST00000535955.5:n.43-3240_43-3239insGGG

ENST00000538626.2:n.191-3240_191-3239insGGG

ENST00000538646.5:c.614_615insGGG

ENST00000540108.1:c.*241_*242insGGG

ENST00000541395.5:c.801_802insGGG

ENST00000541924.5:c.713+545_713+546insGGG

ENST00000543427.5:c.633+625_633+626insGGG

ENST00000544413.2:c.801_802insGGG

ENST00000544574.5:c.73-2366_73-2365insGGG

ENST00000560968.5:n.893+51_893+52insGGG

ENST00000615446.4:c.-257-2011_-257-2010insGGG

ENST00000617366.4:c.586+672_586+673insGGG

NM_000545.5:c.801_802insGGG

NM_001306179.1:c.801_802insGGG

NM_000545.8:c.801_802insGGG

NM_001306179.2:c.801_802insGGG

NM_000545.8(HNF1A):c.801_802insGGG (p.Phe268_Ala269insGly)

Uncertain Significance

PM4_Supporting PM2_Supporting PM1_Supporting

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.801_802insGGG variant in the HNF1 homeobox A gene, HNF1A, is a 3 base pair insertion resulting in the in-frame addition of 1 amino acid at codon 267 (p.Trp267_Phe268insGly) within exon 4 of NM_000545.8. This variant is located within a conserved region of the DNA binding domain (codons 107-174 and 201-280) of HNF1A, which is defined as critical for the protein’s function by the ClinGen MDEP (PM1_Supporting). This variant is also absent from gnomAD v2.1.1 (PM2_Supporting). The c.801_802insGGG variant is predicted to change the length of the protein due to an in-frame insertion of a single amino acid in a nonrepeat region (PM4_Supporting). In summary, c.801_802insGGG 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 1.0, approved 6/4/2021): PM1_Supporting, PM2_Supporting, PM4_Supporting

PM4_Supporting

The c.801_802insGGG variant is predicted to change the length of the protein due to an in-frame insertion of a single amino acid in a nonrepeat region (PM4_Supporting).

PM2_Supporting

This variant is absent from gnomAD.

PM1_Supporting

This variant is located within a conserved region of the DNA binding domain (codons 107-174 and 201-280) of HNF1A, which is defined as critical for the protein’s function by the ClinGen MDEP (PM1_Supporting).

Approved on: 2022-01-21

Published on: 2022-01-21

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