The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
  • No ClinVar Id was directly found from the curated document
  • ClinVar Id was derived from the Allele Registry.


Variant: NM_001306179.1:c.811C>G

CA386966350

1338730 (ClinVar)

Gene: HNF1A
Condition: monogenic diabetes
Inheritance Mode: Autosomal dominant inheritance
UUID: 4113fa42-f346-409e-a460-08c9200229e2

HGVS expressions

NM_001306179.1:c.811C>G
NC_000012.12:g.120994261C>G
CM000674.2:g.120994261C>G
NC_000012.11:g.121432064C>G
CM000674.1:g.121432064C>G
NC_000012.10:g.119916447C>G
NG_011731.2:g.20516C>G
ENST00000257555.11:c.811C>G
ENST00000257555.10:c.811C>G
ENST00000400024.6:c.811C>G
ENST00000402929.5:n.946C>G
ENST00000535955.5:n.43-3230C>G
ENST00000538626.2:n.191-3230C>G
ENST00000538646.5:c.624C>G
ENST00000540108.1:c.*251C>G
ENST00000541395.5:c.811C>G
ENST00000541924.5:c.713+555C>G
ENST00000543427.5:c.633+635C>G
ENST00000544413.2:c.811C>G
ENST00000544574.5:c.73-2356C>G
ENST00000560968.5:n.893+61C>G
ENST00000615446.4:c.-257-2001C>G
ENST00000617366.4:c.586+682C>G
NM_000545.5:c.811C>G
NM_000545.6:c.811C>G
NM_000545.8:c.811C>G
NM_001306179.2:c.811C>G
NM_000545.8(HNF1A):c.811C>G (p.Arg271Gly)

Likely Pathogenic

Met criteria codes 4
PM2_Supporting PM5_Strong PP3 PM1
Not Met criteria codes 1
PP4

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specification: ClinGen Monogenic Diabetes Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines Version 1.1

PDF
Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
Monogenic Diabetes VCEP
The c.811C>G variant in the HNF1 homeobox A gene, HNF1A, causes an amino acid change of arginine to glycine at codon 271 (p. (Arg271Trp) of NM_000545.8. This variant resides in an amino acid within the HNF1α DNA binding domain that directly binds DNA, which is defined as critical for the protein’s function by the ClinGen MDEP (PM1) and is absent from gnomAD v2.1.1 (PM2_Supporting). Two other missense variants, c.811C>T (p.Arg271Trp) and c.812G>A (p.Arg271Gln), have been interpreted as pathogenic by the ClinGen MDEP, and p.Arg271Gly has a greater Grantham distance than both p.Arg271Trp and p.Arg271Gln (PM5_Strong). This variant is predicted to be deleterious by computational evidence, with a REVEL score of 0.911, which is greater than the MDEP VCEP threshold of 0.70 (PP3). This variant was identified in two individual with a clinical history suggestive of HNF1A-MODY (MODY probability calculator result >50%); however, HNF4A was not tested, and PP4 was not applied (internal lab contributors). In summary, c.811C>G meets the criteria to be classified as likely pathogenic for monogenic diabetes. ACMG/AMP criteria applied, as specified by the ClinGen MDEP (specification version 1.1, approved 9/30/2021): PM1, PM2_Supporting, PM5_Strong, PP3.
Met criteria codes
PM2_Supporting
This variant is absent from gnomAD.
PM5_Strong
Two other missense variants, c.811C>T (p.Arg271Trp) and c.812G>A (p.Arg271Gln), have been interpreted as pathogenic by the ClinGen MDEP, and p.Arg271Gly has a greater Grantham distance than both p.Arg271Trp and p.Arg271Gln.
PP3
Predicted deleterious with a REVEL score of 0.911.
PM1
This variant resides in an amino acid within the HNF1α DNA binding domain that directly binds DNA, which is defined as critical for the protein’s function by the ClinGen MDEP.
Not Met criteria codes
PP4
This variant was identified in two individual with a clinical history suggestive of HNF1A-MODY (MODY probability calculator result >50%); however, HNF4A was not tested (internal lab contributors).
Approved on: 2022-04-14
Published on: 2022-07-12
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