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.129_130delinsA

CA2573051033

Gene: HNF1A

Condition: monogenic diabetes

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: efa8ccae-ddb0-45ec-9982-90d6609f3e41

HGVS expressions

NM_001306179.2:c.129_130delinsA

NC_000012.12:g.120978897_120978898delinsA

CM000674.2:g.120978897_120978898delinsA

NC_000012.11:g.121416700_121416701delinsA

CM000674.1:g.121416700_121416701delinsA

NC_000012.10:g.119901083_119901084delinsA

NG_011731.2:g.5152_5153delinsA

ENST00000257555.11:c.129_130delinsA

ENST00000257555.10:c.129_130delinsA

ENST00000400024.6:c.129_130delinsA

ENST00000402929.5:n.264_265delinsA

ENST00000535955.5:n.42+205_42+206delinsA

ENST00000538626.2:n.190+57_190+58delinsA

ENST00000538646.5:c.129_130delinsA

ENST00000540108.1:c.129_130delinsA

ENST00000541395.5:c.129_130delinsA

ENST00000541924.5:c.129_130delinsA

ENST00000543427.5:c.129_130delinsA

ENST00000544413.2:c.129_130delinsA

ENST00000544574.5:c.72+57_72+58delinsA

ENST00000560968.5:n.272_273delinsA

ENST00000615446.4:c.-258+186_-258+187delinsA

ENST00000617366.4:c.129_130delinsA

NM_000545.5:c.129_130delinsA

NM_000545.6:c.129_130delinsA

NM_001306179.1:c.129_130delinsA

NM_000545.8:c.129_130delinsA

Pathogenic

PP1 PVS1 PM2_Supporting

PP4

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.129_130delinsA variant in the HNF1 homeobox A gene, HNF1A, causes a frameshift in the protein at codon 44 (NM_000545.8), adding 111 novel amino acids before encountering a stop codon (p.(Leu44TrpfsTer111). This variant, located in biologically-relevant exon 1 of 10, is predicted to lead to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1; PMID: 23348805). Additionally, this variant segregated with diabetes, with 3 informative meioses in one family with MODY (PP1; PMID: 11692182) and is absent from gnomAD v2.1.1 (PM2_Supporting). This variant was identified in four individuals in one family with diabetes; however, the MODY probability is unable to be calculated due to insufficient clinical information (PMID: 11692182). In summary, c.129_130delinsA meets the criteria to be classified as pathogenic for monogenic diabetes. ACMG/AMP criteria applied, as specified by the ClinGen MDEP (specification version 1.1, approved 9/30.21): PVS1, PP1, PM2_Supporting.

PP1

This variant segregated with diabetes, with three informative meioses in one family with MODY (PP1; PMID: 11692182).

PVS1

This variant, located in biologically-relevant exon 1 of 10 , is predicted to lead to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1; PMID: 23348805).

PM2_Supporting

Absent from gnomAD v2.1.1.

PP4

This variant was identified in an individual with diabetes; however, the MODY probability is unable to be calculated due to insufficient clinical information (PMID: 11692182).

Approved on: 2022-05-04

Published on: 2022-05-04

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