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NM_000283.4(PDE6B):c.2152G>A (p.Asp718Asn) AND not provided

Germline classification:
Conflicting interpretations of pathogenicity (3 submissions)
Last evaluated:
Jan 15, 2024
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:
RCV000297097.31

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]
Observations:
4

Condition(s)

Synonyms:
none provided
Identifiers:
MedGen: C3661900

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000340729Eurofins Ntd Llc (ga)
criteria provided, single submitter

(EGL Classification Definitions 2015)
Uncertain significance
(Mar 23, 2016)
germlineclinical testing

Citation Link,

SCV001154144CeGaT Center for Human Genetics Tuebingen
criteria provided, single submitter

(CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)
Uncertain significance
(May 1, 2019)
germlineclinical testing

Citation Link,

SCV001510447Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Pathogenic
(Jan 15, 2024)
germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyes1not providednot providednot providednot providedclinical testing
not providedgermlineunknown3not providednot providednot providednot providedclinical testing

Citations

PubMed

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

Cost-effective sequence analysis of 113 genes in 1,192 probands with retinitis pigmentosa and Leber congenital amaurosis.

Panneman DM, Hitti-Malin RJ, Holtes LK, de Bruijn SE, Reurink J, Boonen EGM, Khan MI, Ali M, Andréasson S, De Baere E, Banfi S, Bauwens M, Ben-Yosef T, Bocquet B, De Bruyne M, de la Cerda B, Coppieters F, Farinelli P, Guignard T, Inglehearn CF, Karali M, Kjellström U, et al.

Front Cell Dev Biol. 2023;11:1112270. doi: 10.3389/fcell.2023.1112270.

PubMed [citation]
PMID:
36819107
PMCID:
PMC9936074
See all PubMed Citations (4)

Details of each submission

From Eurofins Ntd Llc (ga), SCV000340729.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided3not providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot provided3not providednot providednot provided

From CeGaT Center for Human Genetics Tuebingen, SCV001154144.27

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot provided1not providednot providednot provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001510447.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 718 of the PDE6B protein (p.Asp718Asn). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individuals with autosomal recessive PDE6B-related conditions (PMID: 34906470, 36819107; Invitae). ClinVar contains an entry for this variant (Variation ID: 287073). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt PDE6B protein function with a positive predictive value of 95%. This variant disrupts the p.Asp718 amino acid residue in PDE6B. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 30998820; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 20, 2024