NM_006204.4(PDE6C):c.86G>A (p.Arg29Gln) AND not provided

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Jan 4, 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:: RCV000658572.27

Allele description [Variation Report for NM_006204.4(PDE6C):c.86G>A (p.Arg29Gln)]

NM_006204.4(PDE6C):c.86G>A (p.Arg29Gln)

Gene:

PDE6C:phosphodiesterase 6C [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

10q23.33

Genomic location:

Preferred name:

NM_006204.4(PDE6C):c.86G>A (p.Arg29Gln)

HGVS:

NC_000010.11:g.93612811G>A
NG_016752.1:g.5224G>A
NM_006204.4:c.86G>AMANE SELECT
NP_006195.3:p.Arg29Gln
NC_000010.10:g.95372568G>A

Protein change:

R29Q

Links:

dbSNP: rs781628816

NCBI 1000 Genomes Browser:

rs781628816

Molecular consequence:

NM_006204.4:c.86G>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Zcchc7l protein, partial [Danio rerio]
Zcchc7l protein, partial [Danio rerio]
gi|67677857|gb|AAH96926.1|

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000780349	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Uncertain significance (Nov 1, 2017)	germline	clinical testing	Citation Link,
SCV002161767	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 4, 2024)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 19615668, 21127010, 30080950, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000780349

CeGaT Center for Human Genetics Tuebingen

criteria provided, single submitter

(CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)

Uncertain significance
(Nov 1, 2017)

germline

clinical testing

Citation Link,

SCV002161767

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 4, 2024)

germline

clinical testing

PubMed (4)
[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	1	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

Homozygosity mapping reveals PDE6C mutations in patients with early-onset cone photoreceptor disorders.

Thiadens AA, den Hollander AI, Roosing S, Nabuurs SB, Zekveld-Vroon RC, Collin RW, De Baere E, Koenekoop RK, van Schooneveld MJ, Strom TM, van Lith-Verhoeven JJ, Lotery AJ, van Moll-Ramirez N, Leroy BP, van den Born LI, Hoyng CB, Cremers FP, Klaver CC.

Am J Hum Genet. 2009 Aug;85(2):240-7. doi: 10.1016/j.ajhg.2009.06.016. Epub 2009 Jul 16.

PubMed [citation]

PMID:: 19615668
PMCID:: PMC2725240

Decreased catalytic activity and altered activation properties of PDE6C mutants associated with autosomal recessive achromatopsia.

Grau T, Artemyev NO, Rosenberg T, Dollfus H, Haugen OH, Cumhur Sener E, Jurklies B, Andreasson S, Kernstock C, Larsen M, Zrenner E, Wissinger B, Kohl S.

Hum Mol Genet. 2011 Feb 15;20(4):719-30. doi: 10.1093/hmg/ddq517. Epub 2010 Dec 1.

PubMed [citation]

PMID:: 21127010
PMCID:: PMC3269206

See all PubMed Citations (4)

Details of each submission

From CeGaT Center for Human Genetics Tuebingen, SCV000780349.29

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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002161767.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 29 of the PDE6C protein (p.Arg29Gln). This variant is present in population databases (rs781628816, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with PDE6C-related conditions. ClinVar contains an entry for this variant (Variation ID: 546648). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The glutamine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. This variant disrupts the p.Arg29 amino acid residue in PDE6C. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 19615668, 21127010, 30080950). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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

Last Updated: Oct 20, 2024

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