NM_000283.4(PDE6B):c.2152G>A (p.Asp718Asn) AND Retinitis pigmentosa

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Apr 1, 2021
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:: RCV000332675.9

Allele description [Variation Report for NM_000283.4(PDE6B):c.2152G>A (p.Asp718Asn)]

NM_000283.4(PDE6B):c.2152G>A (p.Asp718Asn)

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.2152G>A (p.Asp718Asn)

HGVS:

NC_000004.12:g.664903G>A
NG_009839.1:g.44330G>A
NM_000283.4:c.2152G>AMANE SELECT
NM_001145291.2:c.2152G>A
NM_001145292.2:c.1315G>A
NM_001350154.3:c.1315G>A
NM_001350155.3:c.997G>A
NM_001379246.1:c.1315G>A
NM_001379247.1:c.1315G>A
NP_000274.2:p.Asp718Asn
NP_000274.3:p.Asp718Asn
NP_001138763.2:p.Asp718Asn
NP_001138764.2:p.Asp439Asn
NP_001337083.1:p.Asp439Asn
NP_001337084.1:p.Asp333Asn
NP_001366175.1:p.Asp439Asn
NP_001366176.1:p.Asp439Asn
NC_000004.11:g.658692G>A
NM_000283.3:c.2152G>A

Protein change:

D333N

Links:

dbSNP: rs150639487

NCBI 1000 Genomes Browser:

rs150639487

Molecular consequence:

NM_000283.4:c.2152G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001145291.2:c.2152G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001145292.2:c.1315G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001350154.3:c.1315G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001350155.3:c.997G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001379246.1:c.1315G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001379247.1:c.1315G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Retinitis pigmentosa (RP)
Synonyms:: Tapetoretinal degeneration
Identifiers:: MONDO: MONDO:0019200; MeSH: D012174; MedGen: C0035334; Orphanet: 791; OMIM: 268000; OMIM: PS268000

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000450827	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Uncertain significance (Jan 12, 2018)	germline	clinical testing	Citation Link,
SCV001950312	Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Apr 1, 2021)	germline	curation	PubMed (2) [See all records that cite these PMIDs] 25741868, 34906470

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000450827

Illumina Laboratory Services, Illumina

criteria provided, single submitter

(ICSL Variant Classification Criteria 13 December 2019)

Uncertain significance
(Jan 12, 2018)

germline

clinical testing

Citation Link,

SCV001950312

Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Apr 1, 2021)

germline

curation

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

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

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

The importance of automation in genetic diagnosis: Lessons from analyzing an inherited retinal degeneration cohort with the Mendelian Analysis Toolkit (MATK).

Zampaglione E, Maher M, Place EM, Wagner NE, DiTroia S, Chao KR, England E, Cmg B, Catomeris A, Nassiri S, Himes S, Pagliarulo J, Ferguson C, Galdikaité-Braziené E, Cole B, Pierce EA, Bujakowska KM.

Genet Med. 2022 Feb;24(2):332-343. doi: 10.1016/j.gim.2021.09.015. Epub 2021 Nov 30.

PubMed [citation]

PMID:: 34906470
PMCID:: PMC9200473

Details of each submission

From Illumina Laboratory Services, Illumina, SCV000450827.3

#	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 in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.

#	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 Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard, SCV001950312.1

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

Description

The p.Asp718Asn variant in PDE6B was identified in an individual with Retinitis pigmentosa, via a collaborative study between the Broad Institute's Center for Mendelian Genomics and the Pierce lab (https://oculargenomics.meei.harvard.edu/labs/pierce-lab/lab-members/). Through a review of available evidence we were able to apply the following criteria: PM2, PP3. Based on this evidence we have classified this variant as a Variant of Uncertain Significance. If you have any questions about the classification please reach out to the Pierce Lab.

#	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: Apr 20, 2025

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