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]

Variant: NM_000545.8(HNF1A):c.306C>T (p.Ala102=)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA482430491

435418 (ClinVar)

Gene: HNF1A

Condition: monogenic diabetes

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: b82f6666-dc04-4ae5-a542-d7babc749bf6

Approved on: 2023-08-13

Published on: 2023-08-13

HGVS expressions

NM_000545.8:c.306C>T

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

NC_000012.12:g.120979074C>T

CM000674.2:g.120979074C>T

NC_000012.11:g.121416877C>T

CM000674.1:g.121416877C>T

NC_000012.10:g.119901260C>T

NG_011731.2:g.5329C>T

ENST00000257555.11:c.306C>T

ENST00000257555.10:c.306C>T

ENST00000400024.6:c.306C>T

ENST00000402929.5:n.441C>T

ENST00000535955.5:n.42+382C>T

ENST00000538626.2:n.190+234C>T

ENST00000538646.5:c.306C>T

ENST00000540108.1:c.306C>T

ENST00000541395.5:c.306C>T

ENST00000541924.5:c.306C>T

ENST00000543427.5:c.306C>T

ENST00000544413.2:c.306C>T

ENST00000544574.5:c.72+234C>T

ENST00000560968.5:n.449C>T

ENST00000615446.4:c.-258+363C>T

ENST00000617366.4:c.306C>T

NM_000545.5:c.306C>T

NM_000545.6:c.306C>T

NM_001306179.1:c.306C>T

NM_001306179.2:c.306C>T

Likely Benign

BP7 BP2 BP4 PM2_Supporting

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.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.

BP7

This synonymous variant is not predicted by SpliceAI to impact splicing and has a phyloP100way score < 2.

BP2

This variant has been observed in unknown phase with a pathogenic HNF1A variant (BP2; internal lab contributor).

BP4

The computational splicing predictor SpliceAI gives a score of 0 for donor gain, suggesting that the variant has no impact on splicing.

PM2_Supporting

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).

Curation History

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