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

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Apr 20, 2022
Review status:
3 stars out of maximum of 4 stars
reviewed by expert panel
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV002250356.3

Allele description [Variation Report for NM_000545.8(HNF1A):c.518_526+37del]

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

Gene:
HNF1A:HNF1 homeobox A [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
12q24.31
Genomic location:
Preferred name:
NM_000545.8(HNF1A):c.518_526+37del
HGVS:
  • NC_000012.12:g.120989024_120989069del
  • NG_011731.2:g.15279_15324del
  • NM_000545.8:c.518_526+37delMANE SELECT
  • NM_001306179.2:c.518_526+37del
  • LRG_522t1:c.518_526+37del46
  • LRG_522:g.15279_15324del
  • NC_000012.11:g.121426827_121426872del
  • NM_000545.5:c.518_526+37del46
Links:
dbSNP: rs386134267
NCBI 1000 Genomes Browser:
rs386134267
Molecular consequence:
  • NM_000545.8:c.518_526+37del - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001306179.2:c.518_526+37del - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Name:
Monogenic diabetes
Identifiers:
MONDO: MONDO:0015967; MedGen: C3888631

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Assertion and evidence details

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Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002520644ClinGen Monogenic Diabetes Variant Curation Expert Panel
reviewed by expert panel

(ClinGen Diabetes ACMG Specifications v1 1)		Likely pathogenic
(Apr 20, 2022) 		germlinecuration

Citation Link

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Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedcuration

Details of each submission

From ClinGen Monogenic Diabetes Variant Curation Expert Panel, SCV002520644.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcurationnot provided

Description

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.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Nov 29, 2022