The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
  • Gene label mismatch: HNF1A vs undefined
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • No CSPEC computed assertion could be determined for this classification!


Variant: NM_000545.8(HNF1A):c.1506_1507dup (p.Tyr503fs)

CA214270

36803 (ClinVar)

Gene: HNF1A
Condition: monogenic diabetes
Inheritance Mode: Autosomal dominant inheritance
UUID: 4057fb8c-5d08-4b7b-b259-9677c306fd09
Approved on: 2025-04-11
Published on: 2025-06-09

HGVS expressions

NM_000545.8:c.1506_1507dup
NM_000545.8(HNF1A):c.1506_1507dup (p.Tyr503fs)
NC_000012.12:g.120999272_120999273dup
CM000674.2:g.120999272_120999273dup
NC_000012.11:g.121437075_121437076dup
CM000674.1:g.121437075_121437076dup
NC_000012.10:g.119921458_119921459dup
NG_011731.2:g.25527_25528dup
ENST00000560968.6:c.*253_*254dup
ENST00000257555.11:c.1506_1507dup
ENST00000257555.10:c.1506_1507dup
ENST00000540108.1:c.*946_*947dup
ENST00000541395.5:c.1506_1507dup
ENST00000543427.5:c.969_970dup
ENST00000544413.2:c.1506_1507dup
ENST00000560968.5:c.1323_1324dup
ENST00000615446.4:c.294_295dup
ENST00000617366.4:c.623_624dup
NM_000545.5:c.1506_1507dup
NM_000545.6:c.1506_1507dup
NM_001306179.1:c.1506_1507dup
NM_001306179.2:c.1506_1507dup
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Likely Pathogenic

Met criteria codes 2
PM2_Supporting PVS1

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specification: ClinGen Monogenic Diabetes Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for HNF1A Version 2.1.0

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
Monogenic Diabetes VCEP
The c.1506_1507dup variant in the HNF1 homeobox A gene, HNF1A, causes a frameshift at codon 503 (NM_000545.8), adding 29 novel amino acids before encountering a stop codon (p.(Tyr503SerfsTer29)). This variant, located in biologically-relevant exon 8 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). This variant is also absent from gnomAD v2.1.1 and v4.1 (PM2_Supporting). In summary, c.1506_1507dup meets the criteria to be classified as likely pathogenic for monogenic diabetes. ACMG/AMP criteria applied, as specified by the ClinGen MDEP (specification version 2.1.0, approved 8/11/23): PVS1, PM2_Supporting.
Met criteria codes
PM2_Supporting
This variant is absent from gnomAD v2.1.1 and v4.1 (PM2_Supporting).
PVS1
This variant, located in biologically-relevant exon 8 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).
Curation History
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