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]

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Variant: NM_001306179.2:c.1501+5G>C

CA386970422

Gene: HNF1A

Condition: monogenic diabetes

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: bf8e2774-d867-482f-8fa9-a6a1247f7bcf

Approved on: 2022-04-18

Published on: 2022-04-18

HGVS expressions

NM_001306179.2:c.1501+5G>C

NC_000012.12:g.120997670G>C

CM000674.2:g.120997670G>C

NC_000012.11:g.121435473G>C

CM000674.1:g.121435473G>C

NC_000012.10:g.119919856G>C

NG_011731.2:g.23925G>C

ENST00000257555.11:c.1501+5G>C

ENST00000257555.10:c.1501+5G>C

ENST00000400024.6:c.1506G>C

ENST00000402929.5:n.2372G>C

ENST00000535955.5:n.222G>C

ENST00000538626.2:n.370G>C

ENST00000538646.5:c.*482G>C

ENST00000540108.1:c.*941+5G>C

ENST00000541395.5:c.1501+5G>C

ENST00000541924.5:c.*520G>C

ENST00000543255.1:n.550G>C

ENST00000543427.5:c.964+5G>C

ENST00000544413.2:c.1501+5G>C

ENST00000544574.5:c.*269G>C

ENST00000560968.5:n.1318+5G>C

ENST00000615446.4:c.289+5G>C

ENST00000617366.4:c.618+5G>C

NM_000545.5:c.1501+5G>C

NM_000545.6:c.1501+5G>C

NM_001306179.1:c.1501+5G>C

NM_000545.8:c.1501+5G>C

Uncertain Significance

PM2_Supporting PP3

PVS1 PP4

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.1501+5G>C variant in the HNF1 homeobox A gene, HNF1A, is predicted to impact splicing in intron 7 of NM_000545.8. This variant is absent from gnomAD v2.1.1 (PM2_Supporting). The computational splicing predictor SpliceAI gives a score of 0.64 for donor loss, predicting that the variant disrupts the donor site of intron 7 of HNF1A (PP3). This variant was identified in an individual(s) with diabetes; however, the calculated MODY probability is <50%, and PP4 cannot be applied (internal lab contributors). In summary, c.1501+5G>C meets the criteria to be classified as a variant of uncertain significance for monogenic diabetes. ACMG/AMP criteria applied, as specified by the ClinGen MDEP (specification version 1.1, approved 9/30/21): PM2_Supporting, PP3.

PM2_Supporting

This variant is absent from gnomAD.

PP3

The computational splicing predictor SpliceAI gives a score of 0.64 for donor loss, predicting that the variant disrupts the donor site of intron 7 of HNF1A.

PVS1

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

PP4

This variant was identified in an individual(s) with diabetes; however, the calculated MODY probability is <50% (internal lab contributors).

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