ClinVar Miner

Submissions for variant NM_000545.8(HNF1A):c.306C>T (p.Ala102=)

dbSNP: rs1486966222
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Monogenic Diabetes Variant Curation Expert Panel RCV003325958 SCV004032118 likely benign Monogenic diabetes 2023-08-13 reviewed by expert panel curation The c.306C>T variant in the HNF1 homeobox A gene, HNF1A, is a synonymous (silent) variant at codon 102 (p.(Ala102=)) of NM_000545.8. This synonymous variant is not predicted by SpliceAI to impact splicing (BP4; BP7) and is at a nucleotide not predicted to be highly conserved (phyloP100way < 2). Additionally, has been observed in unknown phase with a pathogenic HNF1A variant (BP2; internal lab contributor). This variant has an incomputable gnomAD v2.1.1 Popmax filtering allele frequency due to 0 copies in the European non-Finnish subpopulation and 1 copy in the African/African American subpopulation, thereby meeting the ClinGen MDEP threshold criteria for PM2_Supporting (ENF Popmax FAF <= 0.000003 and <= 2 copies in ENF and <=1 copy in any other subpopulation) (PM2_Supporting). In summary, c.306C>T meets the criteria to be classified as likely benign for monogenic diabetes. ACMG/AMP criteria applied, as specified by the ClinGen MDEP (specification version 2.1.0, approved 8/11/2023): BP2, BP4, BP7, PM2_Supporting.
Genetic Services Laboratory, University of Chicago RCV000502226 SCV000595125 likely benign not specified 2015-11-04 criteria provided, single submitter clinical testing
Athena Diagnostics RCV000993270 SCV001146107 likely benign not provided 2019-06-12 criteria provided, single submitter clinical testing
Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic RCV002329193 SCV002601709 benign Maturity onset diabetes mellitus in young criteria provided, single submitter research Mutations in HNF1A gene can predispose to MODY3. It is associated with both micro and macrovascular complications of diabetes, especially cardiovascular complications. Associated with glucosuria. May respond well to sulfonylureas. However, more evidence is required to confer the association of this particular variant rs1486966222 with MODY3.
Ambry Genetics RCV002329193 SCV002753256 likely benign Maturity onset diabetes mellitus in young 2022-10-11 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Labcorp Genetics (formerly Invitae), Labcorp RCV000993270 SCV004377703 likely benign not provided 2023-09-06 criteria provided, single submitter clinical testing

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