The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
  • Gene label mismatch: HNF1A vs undefined
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • No CSPEC computed assertion could be determined for this classification!


Variant: NM_000545.8(HNF1A):c.185A>G (p.Asn62Ser)

CA6831682

447485 (ClinVar)

Gene: HNF1A
Condition: monogenic diabetes
Inheritance Mode: Autosomal dominant inheritance
UUID: 7e62708e-dd55-42f5-9e0a-e6bdb1c0b199
Approved on: 2025-06-09
Published on: 2025-06-09

HGVS expressions

NM_000545.8:c.185A>G
NM_000545.8(HNF1A):c.185A>G (p.Asn62Ser)
NC_000012.12:g.120978953A>G
CM000674.2:g.120978953A>G
NC_000012.11:g.121416756A>G
CM000674.1:g.121416756A>G
NC_000012.10:g.119901139A>G
NG_011731.2:g.5208A>G
ENST00000560968.6:c.185A>G
ENST00000257555.11:c.185A>G
ENST00000257555.10:c.185A>G
ENST00000400024.6:c.185A>G
ENST00000402929.5:n.320A>G
ENST00000535955.5:n.42+261A>G
ENST00000538626.2:n.190+113A>G
ENST00000538646.5:c.185A>G
ENST00000540108.1:c.185A>G
ENST00000541395.5:c.185A>G
ENST00000541924.5:c.185A>G
ENST00000543427.5:c.185A>G
ENST00000544413.2:c.185A>G
ENST00000544574.5:c.72+113A>G
ENST00000560968.5:c.328A>G
ENST00000615446.4:c.-258+242A>G
ENST00000617366.4:c.185A>G
NM_000545.5:c.185A>G
NM_000545.6:c.185A>G
NM_001306179.1:c.185A>G
NM_001306179.2:c.185A>G
More

Benign

Met criteria codes 2
BA1 BP5
Not Met criteria codes 6
BS3 BP4 PS3 PP4 PP3 PM1

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specification: ClinGen Monogenic Diabetes Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for HNF1A Version 2.1.0

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
Monogenic Diabetes VCEP
The c.185A>G variant in the HNF1 homeobox A gene, HNF1A, causes an amino acid change of asparagine to serine at codon 62 (p.(Asn62Ser)) of NM_000545.8. This variant has a Popmax Filtering allele frequency in gnomAD 2.1.1 of 0.00019, which is greater than the MDEP threshold for BA1 (≥0.0001) (BA1). Furthermore, this variant was identified in a patient with an alternate molecular basis for disease (BP5; internal lab contributors). Functional studies demonstrated the p.Asn62Ser protein has 65% transcriptional activity and 70% nuclear localization of wildtype; however, this is between the ClinGen MDEP cutoffs for PS3 and BS3 (PMID: 27899486). This variant has a REVEL score of 0.555, which is between the ClinGen MDEP thresholds for BP4 and PP3, predicting neither a damaging nor benign impact on HNF1A function. This variant was identified in an individual with a clinical history suggestive of HNF1A-MODY (MODY probability calculator result >50%); however, HNF4A was not tested (internal lab contributors). In summary, c.185A>G meets the criteria to be classified as benign for monogenic diabetes. ACMG/AMP criteria applied, as specified by the ClinGen MDEP (specification version 2.1.0, approved 8/11/2023): BA1, BP5.
Met criteria codes
BA1
This variant has a gnomAD Popmax filtering AF greater than 0.0001 (actual value: 0.0001278) for European non-Finnish exomes.
BP5
This variant was identified in an individual with an alternate molecular basis for diabetes (BP5; internal lab contributors).
Not Met criteria codes
BS3
Functional studies demonstrated the p.Asn62Ser protein has 65% transcriptional activity and 70% nuclear localization of wildtype; however, this is between the ClinGen MDEP cutoffs for PS3 and BS3 (PMID: 27899486).
BP4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS3
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 with a clinical history suggestive of HNF1A-MODY (MODY probability calculator result >50%); however, HNF4A was not tested (internal lab contributors).
PP3
This variant has a REVEL score of 0.555, which is between the ClinGen MDEP thresholds for BP4 and PP3, predicting neither a damaging nor benign impact on HNF1A function.
PM1
Not within DNA binding or dimerization domains.
Curation History
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