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_000545.8(HNF1A):c.1720A>G (p.Ser574Gly)

CA214285

36810 (ClinVar)

Gene: HNF1A

Condition: monogenic diabetes

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: e85181fe-8c0d-4882-8417-cd3f34b7ab9f

HGVS expressions

NM_000545.8:c.1720A>G

NM_000545.8(HNF1A):c.1720A>G (p.Ser574Gly)

NC_000012.12:g.120999579A>G

CM000674.2:g.120999579A>G

NC_000012.11:g.121437382A>G

CM000674.1:g.121437382A>G

NC_000012.10:g.119921765A>G

ENST00000257555.11:c.1720A>G

ENST00000257555.10:c.1720A>G

ENST00000540108.1:c.*1160A>G

ENST00000541395.5:c.1813A>G

ENST00000543427.5:c.1183A>G

ENST00000544413.2:c.1741A>G

ENST00000560968.5:n.1537A>G

ENST00000615446.4:c.508A>G

ENST00000617366.4:c.*129A>G

NM_001306179.2:c.1741A>G

Benign

BA1 BP5

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.1720A>G variant in the HNF1 homeobox A gene, HNF1A, causes an amino acid change of serine to glycine at codon 574 (p.(Ser574Gly)) of NM_000545.8. This variant has a Popmax Filtering allele frequency in gnomAD 2.1.1 of 0.996; however, given that the G (Gly) alternate allele has frequencies ≥95% in all subpopulations, we have recalculated the Popmax Filtering allele frequency based on the highest prevalence of the A (Ser) reference allele being found in the African/African-American subpopulation (1144/24164 = 0.0473). The newly calculated Popmax Filtering allele frequency is 0.0447, which is greater than the MDEP threshold for BA1 (≥0.0001) (BA1). Additionally, this variant was identified in a patient with an alternate molecular basis for disease (BP5; internal lab contributors). In summary, c.1720A>G meets the criteria to be classified as benign for monogenic diabetes. ACMG/AMP criteria applied, as specified by the ClinGen MDEP (specification version 1.1, approved 9/30/2021): BA1, BP5.

BA1

This variant has a Popmax Filtering allele frequency in gnomAD 2.1.1 of 0.996; however, given that the G alternate allele has frequencies ≥95% in all subpopulations, we have recalculated the Popmax Filtering allele frequency based on the highest prevalence of the A reference allele being found in the African/African-American subpopulation (1144/24164 = 0.0473). The newly calculated Popmax Filtering allele frequency is 0.0447, which is greater than the MDEP threshold for BA1 (≥0.0001) (BA1).

BP5

This variant was identified in a patient with an alternate molecular basis for disease (internal lab contributors).

Approved on: 2022-04-18

Published on: 2022-04-18

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