NM_000458.4(HNF1B):c.73G>T (p.Val25Leu) AND Renal cysts and diabetes syndrome

Germline classification:: Likely benign (2 submissions)
Last evaluated:: Apr 27, 2017
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000030533.15

Allele description [Variation Report for NM_000458.4(HNF1B):c.73G>T (p.Val25Leu)]

NM_000458.4(HNF1B):c.73G>T (p.Val25Leu)

Gene:

HNF1B:HNF1 homeobox B [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

17q12

Genomic location:

Preferred name:

NM_000458.4(HNF1B):c.73G>T (p.Val25Leu)

HGVS:

NC_000017.11:g.37744812C>A
NG_013019.2:g.5295G>T
NM_000458.4:c.73G>TMANE SELECT
NM_001165923.4:c.73G>T
NM_001304286.2:c.73G>T
NP_000449.1:p.Val25Leu
NP_001159395.1:p.Val25Leu
NP_001291215.1:p.Val25Leu
NC_000017.10:g.36104803C>A
NM_000458.2:c.73G>T
NM_000458.3:c.73G>T

Protein change:

V25L

Links:

dbSNP: rs139107479

NCBI 1000 Genomes Browser:

rs139107479

Molecular consequence:

NM_000458.4:c.73G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001165923.4:c.73G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001304286.2:c.73G>T - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Renal cysts and diabetes syndrome (RCAD)
Synonyms:: Maturity-onset diabetes of the young, type 5; MODY type 5; Hyperuricemic nephropathy, familial juvenile, atypical; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0007669; MedGen: C0431693; Orphanet: 93111; OMIM: 137920

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000053204	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	likely benign (Aug 18, 2011)	germline	curation, clinical testing	PubMed (3) [See all records that cite these PMIDs] 20603712, 15930087, 19389850 Citation Link,
SCV000402436	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Likely benign (Apr 27, 2017)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000053204

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

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

likely benign
(Aug 18, 2011)

germline

curation, clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Citation Link,

SCV000402436

Illumina Laboratory Services, Illumina

criteria provided, single submitter

(ICSL Variant Classification Criteria 13 December 2019)

Likely benign
(Apr 27, 2017)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	3	not provided	not provided	3	not provided	curation
not provided	germline	unknown	2	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Renal malformations associated with mutations of developmental genes: messages from the clinic.

Adalat S, Bockenhauer D, Ledermann SE, Hennekam RC, Woolf AS.

Pediatr Nephrol. 2010 Nov;25(11):2247-55. doi: 10.1007/s00467-010-1578-y. Epub 2010 Jul 6. Review.

PubMed [citation]

PMID:: 20603712
PMCID:: PMC2937138

Mutations in hepatocyte nuclear factor-1beta and their related phenotypes.

Edghill EL, Bingham C, Ellard S, Hattersley AT.

J Med Genet. 2006 Jan;43(1):84-90. Epub 2005 Jun 1.

PubMed [citation]

PMID:: 15930087
PMCID:: PMC2564507

See all PubMed Citations (3)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000053204.2

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

Description

"Found in 1 pt; Father also carried variant but showed no signs of renal disease (authors note that he had never had a renal ultrasound). Authors consider this a rare variant of unknown pathogenicity.": PubMed [ID: 15930087]
"From text: "In our family, the child has renal cysts and his father has diabetes and a smaller left kidney with scarring." Found in 3 out of 302 control chromosomes tested (see pbGP), author concluded this to be a polymorphism.": PubMed [ID: 19389850]

Description

Converted during submission to Likely benign.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	1	not provided	not provided		1	not provided	not provided	not provided
2	germline	yes	2	not provided	not provided		2	not provided	not provided	not provided
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

Co-occurrences

#	Zygosity	Alleles	Number of Observations
3	Homozygote	GCK:c.106C>T, HNF4A:c.116-5C>T, TCF1:c.51C>G, TCF1:c.1501+7G>A, TCF1:c.1720A>G, TCF1:c.293C>T	1
4	SingleHeterozygote	HNF4A:c.116-5C>T, TCF1:c.1720A>G	1

From Illumina Laboratory Services, Illumina, SCV000402436.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

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). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely 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: Apr 20, 2024

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