The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
  • No ClinVar Id was directly found from the curated document
  • ClinVar Id was derived from the Allele Registry.
  • 'cspec' property is found but contains no ID!

  • See Evidence submitted by expert panel for details.

Variant: NM_001306179.2:c.526+1G>T

CA386960844

1746441 (ClinVar)

Gene: HNF1A
Condition: monogenic diabetes
Inheritance Mode: Autosomal dominant inheritance
UUID: 783da021-ae5d-40fd-8fc1-17103a557156
Approved on: 2023-12-02
Published on: 2023-12-02

HGVS expressions

NM_001306179.2:c.526+1G>T
NC_000012.12:g.120989033G>T
CM000674.2:g.120989033G>T
NC_000012.11:g.121426836G>T
CM000674.1:g.121426836G>T
NC_000012.10:g.119911219G>T
NG_011731.2:g.15288G>T
ENST00000257555.11:c.526+1G>T
ENST00000257555.10:c.526+1G>T
ENST00000400024.6:c.526+1G>T
ENST00000402929.5:n.661+1G>T
ENST00000535955.5:n.43-8458G>T
ENST00000538626.2:n.191-8458G>T
ENST00000538646.5:c.526+1G>T
ENST00000540108.1:c.327-4487G>T
ENST00000541395.5:c.526+1G>T
ENST00000541924.5:c.526+1G>T
ENST00000543427.5:c.526+1G>T
ENST00000544413.2:c.526+1G>T
ENST00000544574.5:c.73-7584G>T
ENST00000560968.5:c.669+1G>T
ENST00000615446.4:c.-257-7229G>T
ENST00000617366.4:c.526+1G>T
NM_000545.5:c.526+1G>T
NM_000545.6:c.526+1G>T
NM_001306179.1:c.526+1G>T
NM_000545.8:c.526+1G>T
NM_000545.8(HNF1A):c.526+1G>T
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Pathogenic

Met criteria codes 3
PM2_Supporting PVS1 PS1_Supporting
Not Met criteria codes 2
PP4 PP1

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
Monogenic Diabetes VCEP
The c.526+1G>T variant in the HNF1 homeobox A gene, HNF1A, is predicted to remove a canonical splice donor site in intron 2 of NM_000545.8. This variant is predicted to cause loss of part of exon 2, leading to nonsense-mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1, PMID: 23348805). This variant is absent from gnomAD v2.1.1 (PM2_Supporting). The HNF1A(NM_000545.8):c.526+1G>A and c.526+1G>C variants at the same canonical nucleotide have been classified as pathogenic for monogenic diabetes by the ClinGen MDEP, and c.526+1G>T has a similar predicted impact by Splice AI (donor loss 100% and donor gain at -33bp 65%) (PS1_Supporting). This variant was identified in an individual with diabetes; however, the MODY probability is unable to be calculated due to lack of clinical information.  This variant segregated with diabetes with one informative meioses in a single family; however, this does not meet the thresholds for PP1 set by the ClinGen MDEP.  In summary, c.526+1G>T meets the criteria to be classified as pathogenic for monogenic diabetes. ACMG/AMP criteria applied, as specified by the ClinGen MDEP (specification version 2.1.1, approved 8/11/2023): PVS1, PS1_Supporting, PM2_Supporting.    
Met criteria codes
PM2_Supporting
This variant is absent from gnomAD v2.1.1.
PVS1
This variant is predicted to cause loss of part exon 2 , leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism.
PS1_Supporting
The HNF1A(NM_000545.8):c.526+1G>A and c.526+1G>C variants at the same canonical nucleotide have been classified as pathogenic for monogenic diabetes by the ClinGen MDEP, and c.526+1G>T has a similar predicted impact by Splice AI (donor loss 100% and donor gain at -33 bp 65%) (PS1_Supporting).
Not Met criteria codes
PP4
This variant was identified in an individual with diabetes; however, the MODY probability is unable to be calculated due to lack of clinical information.
PP1
This variant segregated with diabetes with one informative meioses in a single family; however, this does not meet the thresholds for PP1 set by the ClinGen MDEP.
Curation History
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