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]

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Variant: NM_000545.8(HNF1A):c.518_526+37del

CA214310

36823 (ClinVar)

Gene: HNF1A

Condition: monogenic diabetes

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: e52b92ef-05ab-40b4-ac5d-66c22a950f29

Approved on: 2022-04-20

Published on: 2022-04-20

HGVS expressions

NM_000545.8:c.518_526+37del

NM_000545.8(HNF1A):c.518_526+37del

NC_000012.12:g.120989024_120989069del

CM000674.2:g.120989024_120989069del

NC_000012.11:g.121426827_121426872del

CM000674.1:g.121426827_121426872del

NC_000012.10:g.119911210_119911255del

NG_011731.2:g.15279_15324del

ENST00000257555.11:c.518_526+37del

ENST00000257555.10:c.518_526+37del

ENST00000400024.6:c.518_526+37del

ENST00000402929.5:n.653_661+37del

ENST00000535955.5:n.43-8467_43-8422del

ENST00000538626.2:n.191-8467_191-8422del

ENST00000538646.5:c.518_526+37del

ENST00000540108.1:c.327-4496_327-4451del

ENST00000541395.5:c.518_526+37del

ENST00000541924.5:c.518_526+37del

ENST00000543427.5:c.518_526+37del

ENST00000544413.2:c.518_526+37del

ENST00000544574.5:c.73-7593_73-7548del

ENST00000560968.5:n.661_669+37del

ENST00000615446.4:c.-257-7238_-257-7193del

ENST00000617366.4:c.518_526+37del

NM_000545.5:c.518_526+37del

NM_000545.6:c.518_526+37del

NM_001306179.1:c.518_526+37del

NM_001306179.2:c.518_526+37del

Likely Pathogenic

The Expert Panel has overridden the computationally generated classification - "Uncertain Significance - Insufficient Evidence"

PM2_Supporting PVS1

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.518_526+37del variant in the HNF1 homeobox A gene, HNF1A, is a 46 base pair deletion that removes a canonical splice donor site in intron 2 of NM_000545.8. This variant is predicted to cause skipping of biologically-relevant exon 2 of 10, resulting in a frameshift, leading 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 (PM2_Supporting). In summary, c.518_526+37del meets the criteria to be classified as likely pathogenic for monogenic diabetes. ACMG/AMP criteria applied, as specified by the ClinGen MDEP (Specification version For HNF1A: version 1.1, Approved 9/30/21): PVS1, PM2_Supporting.

PM2_Supporting

This variant is absent from gnomAD v2.1.1.

PVS1

This variant is predicted to cause skipping of biologically-relevant exon 2 of 10, resulting in a frameshift, leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism

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