NM_175914.5(HNF4A):c.426+6G>A AND Maturity-onset diabetes of the young type 1

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: Apr 27, 2017
Review status:: criteria provided, conflicting classifications

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000030022.8

Allele description [Variation Report for NM_175914.5(HNF4A):c.426+6G>A]

NM_175914.5(HNF4A):c.426+6G>A

Gene:

HNF4A:hepatocyte nuclear factor 4 alpha [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

20q13.12

Genomic location:

Preferred name:

NM_175914.5(HNF4A):c.426+6G>A

HGVS:

NC_000020.11:g.44413806G>A
NG_009818.1:g.63006G>A
NM_000457.6:c.492+6G>A
NM_001030003.3:c.426+6G>A
NM_001030004.3:c.426+6G>A
NM_001258355.2:c.471+6G>A
NM_001287182.2:c.417+6G>A
NM_001287183.2:c.417+6G>A
NM_001287184.2:c.417+6G>A
NM_175914.5:c.426+6G>AMANE SELECT
NM_178849.3:c.492+6G>A
NM_178850.3:c.492+6G>A
LRG_483t1:c.426+6G>A
LRG_483t2:c.492+6G>A
LRG_483:g.63006G>A
NC_000020.10:g.43042446G>A
NM_000457.3:c.492+6G>A
NM_000457.4:c.492+6G>A
NM_175914.3:c.426+6G>A
NM_175914.4:c.426+6G>A

Links:

dbSNP: rs182980547

NCBI 1000 Genomes Browser:

rs182980547

Molecular consequence:

NM_000457.6:c.492+6G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001030003.3:c.426+6G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001030004.3:c.426+6G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001258355.2:c.471+6G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001287182.2:c.417+6G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001287183.2:c.417+6G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001287184.2:c.417+6G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_175914.5:c.426+6G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_178849.3:c.492+6G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_178850.3:c.492+6G>A - intron variant - [Sequence Ontology: SO:0001627]

Observations:

Condition(s)

Name:: Maturity-onset diabetes of the young type 1
Synonyms:: MILD JUVENILE DIABETES MELLITUS; MODY type 1; Diabetes mellitus MODY type 1; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0007452; MedGen: C1852093; Orphanet: 552; OMIM: 125850

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GK [Gracilinanus agilis]
GK [Gracilinanus agilis]
Gene ID:123241609

Gene
ELOVL3 [Taeniopygia guttata]
ELOVL3 [Taeniopygia guttata]
Gene ID:115495846

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000052677	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	uncertain (Aug 18, 2011)	germline	curation, clinical testing	Citation Link,
SCV001302277	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Benign (Apr 27, 2017)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 26467025, 26059258 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000052677

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

uncertain
(Aug 18, 2011)

germline

curation, clinical testing

Citation Link,

SCV001302277

Illumina Laboratory Services, Illumina

criteria provided, single submitter

(ICSL Variant Classification Criteria 13 December 2019)

Benign
(Apr 27, 2017)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	1	not provided	not provided	not provided	not provided	curation
not provided	germline	unknown	4	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

A Standardized DNA Variant Scoring System for Pathogenicity Assessments in Mendelian Disorders.

Karbassi I, Maston GA, Love A, DiVincenzo C, Braastad CD, Elzinga CD, Bright AR, Previte D, Zhang K, Rowland CM, McCarthy M, Lapierre JL, Dubois F, Medeiros KA, Batish SD, Jones J, Liaquat K, Hoffman CA, Jaremko M, Wang Z, Sun W, Buller-Burckle A, et al.

Hum Mutat. 2016 Jan;37(1):127-34. doi: 10.1002/humu.22918. Epub 2015 Oct 29.

PubMed [citation]

PMID:: 26467025
PMCID:: PMC4737317

Characteristics of maturity onset diabetes of the young in a large diabetes center.

Chambers C, Fouts A, Dong F, Colclough K, Wang Z, Batish SD, Jaremko M, Ellard S, Hattersley AT, Klingensmith G, Steck AK.

Pediatr Diabetes. 2016 Aug;17(5):360-7. doi: 10.1111/pedi.12289. Epub 2015 Jun 8.

PubMed [citation]

PMID:: 26059258
PMCID:: PMC4934136

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000052677.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	curation	not provided
2	not provided	not provided	not provided	not provided	clinical testing	not provided
3	not provided	not provided	not provided	not provided	clinical testing	not provided
4	not provided	not provided	not provided	not provided	clinical testing	not provided
5	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

Converted during submission to Uncertain significance.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	Blood	assert pathogenicity		not provided	not provided	not provided	not provided
2	germline	unknown	not provided	Blood	assert pathogenicity		not provided	not provided	not provided	See 2
3	germline	unknown	not provided	Blood	assert pathogenicity		not provided	not provided	not provided	See 3
4	germline	unknown	not provided	Blood	assert pathogenicity		not provided	not provided	not provided	See 4
5	germline	unknown	not provided	Blood	assert pathogenicity		not provided	not provided	not provided	See 5

Co-occurrences

#	Zygosity	Alleles	Number of Observations
2	SingleHeterozygote	GCK:c.1253+8C>T, HNF4A:c.116-5C>T, HNF4A:c.201C>T, TCF1:c.79A>C, TCF1:c.51C>G, TCF1:c.1545G>A, TCF1:c.1460G>A, TCF1:c.1375C>T, TCF1:c.864G>C, TCF1:c.1501+7G>A, TCF1:c.1720A>G, TCF1:c.811C>T	1
3	SingleHeterozygote	GCK:c.1253+8C>T, HNF4A:c.201C>T, HNF4A:c.116-5C>T, TCF1:c.864G>C, TCF1:c.1720A>G	1
4	SingleHeterozygote	GCK:c.1253+8C>T, HNF4A:c.201C>T, HNF4A:c.116-5C>T, TCF1:c.864G>C, TCF1:c.1720A>G	1
5	SingleHeterozygote	HNF4A:c.201C>T, HNF4A:c.116-5C>T, IPF1:c.725C>T, TCF1:c.864G>C, TCF1:c.1501+7G>A, TCF1:c.1460G>A, TCF1:c.1375C>T, TCF1:c.1720A>G	1

From Illumina Laboratory Services, Illumina, SCV001302277.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Aug 4, 2024

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