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.42G>A (p.Ala14=)

CA6831657

307456 (ClinVar)

Gene: HNF1A

Condition: monogenic diabetes

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: c7c3bc15-23b4-4a8b-bb58-0d6530f1f56a

Approved on: 2022-03-30

Published on: 2022-03-30

HGVS expressions

NM_000545.8:c.42G>A

NM_000545.8(HNF1A):c.42G>A (p.Ala14=)

NC_000012.12:g.120978810G>A

CM000674.2:g.120978810G>A

NC_000012.11:g.121416613G>A

CM000674.1:g.121416613G>A

NC_000012.10:g.119900996G>A

NG_011731.2:g.5065G>A

ENST00000257555.11:c.42G>A

ENST00000257555.10:c.42G>A

ENST00000400024.6:c.42G>A

ENST00000402929.5:n.177G>A

ENST00000535955.5:n.42+118G>A

ENST00000538626.2:n.160G>A

ENST00000538646.5:c.42G>A

ENST00000540108.1:c.42G>A

ENST00000541395.5:c.42G>A

ENST00000541924.5:c.42G>A

ENST00000543427.5:c.42G>A

ENST00000544413.2:c.42G>A

ENST00000544574.5:c.42G>A

ENST00000560968.5:n.185G>A

ENST00000615446.4:c.-258+99G>A

ENST00000617366.4:c.42G>A

NM_000545.5:c.42G>A

NM_000545.6:c.42G>A

NM_001306179.1:c.42G>A

NM_001306179.2:c.42G>A

Uncertain Significance

BP7

BS1 PM2

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.42G>A variant in the HNF1 homeobox A gene, HNF1A, is a synonymous (silent) variant at codon 14 (p.Ala14=) of NM_000545.8. This synonymous variant is not predicted by SpliceAI to impact splicing (BP7). The Popmax Filtering allele frequency of the c.42G>A variant in gnomAD v2.1.1 is 0.00002233, which falls between ClinGen MDEP-established cutoffs for PM2_Supporting and BS1; thus, neither criterion will be applied. In summary, c.42G>A 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 9/30/2021): BP7

BP7

This synonymous variant is not predicted by SpliceAI to impact splicing (BP7).

BS1

This variant has a Popmax filtering allele frequency of less than 0.00003 (actual value = 0.00002233)

PM2

This variant has a major allele frequency in gnomAD greater than 0.00002 (European non-Finnish=0.00003950 (5 copies) + 3 copies in the African population).

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