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NM_000283.4(PDE6B):c.1669C>T (p.His557Tyr) AND Retinitis pigmentosa 40

Germline classification:
Likely pathogenic (2 submissions)
Last evaluated:
May 22, 2022
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
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:
RCV000013985.19

Allele description [Variation Report for NM_000283.4(PDE6B):c.1669C>T (p.His557Tyr)]

NM_000283.4(PDE6B):c.1669C>T (p.His557Tyr)

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.1669C>T (p.His557Tyr)
HGVS:
  • NC_000004.12:g.662188C>T
  • NG_009839.1:g.41615C>T
  • NM_000283.4:c.1669C>TMANE SELECT
  • NM_001145291.2:c.1669C>T
  • NM_001145292.2:c.832C>T
  • NM_001350154.3:c.832C>T
  • NM_001350155.3:c.514C>T
  • NM_001379246.1:c.832C>T
  • NM_001379247.1:c.832C>T
  • NP_000274.2:p.His557Tyr
  • NP_000274.3:p.His557Tyr
  • NP_001138763.2:p.His557Tyr
  • NP_001138764.2:p.His278Tyr
  • NP_001337083.1:p.His278Tyr
  • NP_001337084.1:p.His172Tyr
  • NP_001366175.1:p.His278Tyr
  • NP_001366176.1:p.His278Tyr
  • NC_000004.11:g.655977C>T
  • NM_000283.3:c.1669C>T
  • P35913:p.His557Tyr
Protein change:
H172Y; HIS557TYR
Links:
UniProtKB: P35913#VAR_006050; OMIM: 180072.0004; dbSNP: rs121918581
NCBI 1000 Genomes Browser:
rs121918581
Molecular consequence:
  • NM_000283.4:c.1669C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001145291.2:c.1669C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001145292.2:c.832C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001350154.3:c.832C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001350155.3:c.514C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001379246.1:c.832C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001379247.1:c.832C>T - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

Name:
Retinitis pigmentosa 40 (RP40)
Identifiers:
MONDO: MONDO:0013429; MedGen: C3151107; Orphanet: 791; OMIM: 613801

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000034232OMIM
no assertion criteria provided
Pathogenic
(Jun 1, 1993) 		germlineliterature only

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

SCV0025218443billion
criteria provided, single submitter

(ACMG Guidelines, 2015)		Likely pathogenic
(May 22, 2022) 		germlineclinical testing

PubMed (5)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyes1not providednot provided1not providedclinical testing
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

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

Mutation spectrum of the gene encoding the beta subunit of rod phosphodiesterase among patients with autosomal recessive retinitis pigmentosa.

McLaughlin ME, Ehrhart TL, Berson EL, Dryja TP.

Proc Natl Acad Sci U S A. 1995 Apr 11;92(8):3249-53.

PubMed [citation]
PMID:
7724547
PMCID:
PMC42143
See all PubMed Citations (6)

Details of each submission

From OMIM, SCV000034232.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (1)

Description

Using SSCP analysis to study DNA from a patient with autosomal recessive retinitis pigmentosa (RP40; 613801), McLaughlin et al. (1993) identified a C-to-T transition at position 19876 in exon 13 of the PDE6B gene, resulting in a his557-to-tyr (H557Y) substitution.

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

From 3billion, SCV002521844.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (5)

Description

The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.003%). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.99; 3Cnet: 3CNET). Same nucleotide change resulting in same amino acid change has been previously reported to be associated with PDE6B related disorder (ClinVar ID: VCV000013106 / PMID: 7724547). The variant has been reported to be in trans with a pathogenic variant as either compound heterozygous or homozygous in at least one similarly affected unrelated individual (PMID: 25827439, 26155838). A different missense change at the same codon (p.His557Arg) has been reported to be associated with PDE6B related disorder (ClinVar ID: VCV000636186 / PMID: 30718709). Therefore, this variant is classified as likely pathogenic according to the recommendation of ACMG/AMP guideline.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyes1not providednot provided1not providednot providednot provided

Last Updated: Sep 29, 2024