NM_000545.8(HNF1A):c.526+1G>A AND not provided

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Jan 25, 2024
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:: RCV001049923.13

Allele description

NM_000545.8(HNF1A):c.526+1G>A

Gene:

HNF1A:HNF1 homeobox A [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

12q24.31

Genomic location:

Preferred name:

NM_000545.8(HNF1A):c.526+1G>A

HGVS:

NC_000012.12:g.120989033G>A
NG_011731.2:g.15288G>A
NM_000545.8:c.526+1G>AMANE SELECT
NM_001306179.2:c.526+1G>A
NM_001406915.1:c.526+1G>A
LRG_522t1:c.526+1G>A
LRG_522:g.15288G>A
NC_000012.11:g.121426836G>A
NM_000545.5:c.526+1G>A
NM_000545.6:c.526+1G>A

Links:

dbSNP: rs1364708195

NCBI 1000 Genomes Browser:

rs1364708195

Molecular consequence:

NM_000545.8:c.526+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001306179.2:c.526+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406915.1:c.526+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

Clear Turn Off Turn On

Fictibacillus nanhaiensis strain DSM 23009, whole genome shotgun sequencing proj...
Fictibacillus nanhaiensis strain DSM 23009, whole genome shotgun sequencing project
gi|1995406055|gb|JAFHKR000000000.1| R010000000

Nucleotide
bacillomycin D hybrid PKS/NRPS BamA [Bacillus velezensis]
bacillomycin D hybrid PKS/NRPS BamA [Bacillus velezensis]
gi|505052851|ref|WP_015239953.1|

Protein
os08e11.x5 NCI_CGAP_Lu5 Homo sapiens cDNA clone IMAGE:1604780 3', mRNA sequence
os08e11.x5 NCI_CGAP_Lu5 Homo sapiens cDNA clone IMAGE:1604780 3', mRNA sequence
gi|5439722|gnl|dbEST|2908263|gb|AI8 .1|

Nucleotide
yf17f10.s1 Soares fetal liver spleen 1NFLS Homo sapiens cDNA clone IMAGE:127147 ...
yf17f10.s1 Soares fetal liver spleen 1NFLS Homo sapiens cDNA clone IMAGE:127147 3', mRNA sequence
gi|760064|gnl|dbEST|178437|gb|R0814

Nucleotide
Hypnum resupinatum voucher Hyp 52 internal transcribed spacer 1 and 5.8S ribosom...
Hypnum resupinatum voucher Hyp 52 internal transcribed spacer 1 and 5.8S ribosomal RNA gene, partial sequence
gi|295001496|gb|GU969017.1|

Nucleotide

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001214002	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 25, 2024)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 16199547, 15928245, 18003757, 11272211, 21242637, 31754975, 28492532
SCV002067336	Genetic Services Laboratory, University of Chicago	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jun 18, 2019)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002504369	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Apr 9, 2020)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001214002

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 25, 2024)

germline

clinical testing

PubMed (7)
[See all records that cite these PMIDs]

SCV002067336

Genetic Services Laboratory, University of Chicago

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Jun 18, 2019)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV002504369

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Apr 9, 2020)

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	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]

PMID:: 16199547
PMCID:: PMC1735933

Half of clinically defined maturity-onset diabetes of the young patients in Denmark do not have mutations in HNF4A, GCK, and TCF1.

Johansen A, Ek J, Mortensen HB, Pedersen O, Hansen T.

J Clin Endocrinol Metab. 2005 Aug;90(8):4607-14. Epub 2005 May 31.

PubMed [citation]

PMID:: 15928245

See all PubMed Citations (8)

Details of each submission

From Invitae, SCV001214002.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (7)

Description

This sequence change affects a donor splice site in intron 2 of the HNF1A gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in HNF1A are known to be pathogenic (PMID: 15928245, 18003757). This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individuals with maturity-onset diabetes of the young (PMID: 11272211, 21242637, 31754975). This variant is also known as IVS2+1G>A. ClinVar contains an entry for this variant (Variation ID: 846588). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.

#	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

From Genetic Services Laboratory, University of Chicago, SCV002067336.1

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

Description

DNA sequence analysis of the HNF1A gene demonstrated a sequence change in the canonical splice donor site of intron 2, c.526+1G>A. This sequence change is absent from large population databases such as ExAC and gnomAD. This pathogenic sequence change has been previously described in three affected individuals from a family with maturity-onset diabetes of the young type 3 (MODY3) (PMID: 11272211). This pathogenic sequence change is predicted to affect normal splicing of the HNF1A gene, leading to an abnormal protein, which may be degraded, or may lead to production of a truncated HNF1A protein with potentially abnormal function. " DNA sequence analysis of the HNF1A gene demonstrated a sequence change in the canonical splice donor site of intron 2, c.526+1G>A. This sequence change is absent from large population databases such as ExAC and gnomAD. This pathogenic sequence change has been previously described in three affected individuals from a family with maturity-onset diabetes of the young type 3 (MODY3) (PMID: 11272211). This pathogenic sequence change is predicted to affect normal splicing of the HNF1A gene, leading to an abnormal protein, which may be degraded, or may lead to production of a truncated HNF1A protein with potentially abnormal function.

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

From GeneDx, SCV002504369.2

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

Description

Canonical splice site variant predicted to result in a null allele in a gene for which loss-of-function is a known mechanism of disease; Identified in individuals with early onset diabetes in published literature (Frayling et al., 2001; Jeannot et al., 2010); This variant is associated with the following publications: (PMID: 21242637, 25525159, 11272211, 31754975, 20393147, 32238361, 16496320)

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

Last Updated: Feb 20, 2024

ClinVar

Relating variation to medicine