The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

  • See Evidence submitted by expert panel for details.

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

CA214310

36823 (ClinVar)

Gene: HNF1A
Condition: monogenic diabetes
Inheritance Mode: Autosomal dominant inheritance
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"
Met criteria codes 2
PM2_Supporting PVS1

Evidence Links 0

Expert Panel

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.
Met criteria codes
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
The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.
¤ Powered by BCM's Genboree.