NM_000283.4(PDE6B):c.2193+1G>A AND not provided

Germline classification:: Pathogenic (5 submissions)
Last evaluated:: Jan 8, 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:: RCV000723948.15

Allele description [Variation Report for NM_000283.4(PDE6B):c.2193+1G>A]

NM_000283.4(PDE6B):c.2193+1G>A

Gene:

PDE6B:phosphodiesterase 6B [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

4p16.3

Genomic location:

Preferred name:

NM_000283.4(PDE6B):c.2193+1G>A

HGVS:

NC_000004.12:g.664945G>A
NG_009839.1:g.44372G>A
NG_009839.2:g.44374G>A
NM_000283.4:c.2193+1G>AMANE SELECT
NM_001145291.2:c.2193+1G>A
NM_001145292.2:c.1356+1G>A
NM_001350154.3:c.1356+1G>A
NM_001350155.3:c.1038+1G>A
NM_001379246.1:c.1356+1G>A
NM_001379247.1:c.1356+1G>A
NC_000004.11:g.658734G>A
NM_000283.3:c.2193+1G>A

Links:

dbSNP: rs727504075

NCBI 1000 Genomes Browser:

rs727504075

Molecular consequence:

NM_000283.4:c.2193+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001145291.2:c.2193+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001145292.2:c.1356+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001350154.3:c.1356+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001350155.3:c.1038+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001379246.1:c.1356+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001379247.1:c.1356+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000203224	Eurofins Ntd Llc (ga)	criteria provided, single submitter (EGL Classification Definitions 2015)	Pathogenic (Oct 8, 2015)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link,
SCV001213695	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 8, 2024)	germline	clinical testing	PubMed (9) [See all records that cite these PMIDs] 16199547, 8394174, 8595886, 22334370, 7724547, 25097241, 28041643, 28224992, 28492532
SCV001920902	Clinical Genetics, Academic Medical Center - VKGL Data-share Consensus See additional submitters Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	no assertion criteria provided	Pathogenic	germline	clinical testing
SCV001956724	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ - VKGL Data-share Consensus See additional submitters Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	no assertion criteria provided	Pathogenic	germline	clinical testing
SCV001972444	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center - VKGL Data-share Consensus See additional submitters Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	no assertion criteria provided	Pathogenic	germline	clinical testing

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	3	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

Recessive mutations in the gene encoding the beta-subunit of rod phosphodiesterase in patients with retinitis pigmentosa.

McLaughlin ME, Sandberg MA, Berson EL, Dryja TP.

Nat Genet. 1993 Jun;4(2):130-4.

PubMed [citation]

PMID:: 8394174

See all PubMed Citations (9)

Details of each submission

From Eurofins Ntd Llc (ga), SCV000203224.7

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

#	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		3	not provided	not provided	not provided

From Invitae, SCV001213695.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (9)

Description

This sequence change affects a donor splice site in intron 18 of the PDE6B 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 PDE6B are known to be pathogenic (PMID: 8394174, 8595886, 22334370). This variant is present in population databases (rs727504075, gnomAD 0.01%). Disruption of this splice site has been observed in individuals with autosomal recessive retinitis pigmentosa or retinal dystrophy (PMID: 7724547, 25097241, 28041643, 28224992). It has also been observed to segregate with disease in related individuals. This variant is also known as a G>A transition at position 22624. ClinVar contains an entry for this variant (Variation ID: 167440). 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 Clinical Genetics, Academic Medical Center - VKGL Data-share Consensus, SCV001920902.1

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

#	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 Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ - VKGL Data-share Consensus, SCV001956724.1

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

#	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 Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center - VKGL Data-share Consensus, SCV001972444.1

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

#	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: Mar 30, 2024

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