NM_000180.4(GUCY2D):c.2988C>G (p.Tyr996Ter) AND multiple conditions

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Feb 29, 2020
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:: RCV001056225.5

Allele description

NM_000180.4(GUCY2D):c.2988C>G (p.Tyr996Ter)

Gene:

GUCY2D:guanylate cyclase 2D, retinal [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

17p13.1

Genomic location:

Preferred name:

NM_000180.4(GUCY2D):c.2988C>G (p.Tyr996Ter)

HGVS:

NC_000017.11:g.8015786C>G
NG_009092.1:g.18117C>G
NM_000180.4:c.2988C>GMANE SELECT
NP_000171.1:p.Tyr996Ter
NC_000017.10:g.7919104C>G
NM_000180.3:c.2988C>G

Protein change:

Y996*

Links:

dbSNP: rs1975957350

NCBI 1000 Genomes Browser:

rs1975957350

Molecular consequence:

NM_000180.4:c.2988C>G - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Cone-rod dystrophy 6 (CORD6)
Synonyms:: Retinal cone dystrophy 2; Cone dystrophy progressive
Identifiers:: MONDO: MONDO:0011143; MedGen: C1866293; Orphanet: 1872; OMIM: 601777

Name:: Leber congenital amaurosis 1 (LCA1)
Synonyms:: AMAUROSIS CONGENITA OF LEBER I; Congenital absence of the rods and cones; Leber's congenital tapetoretinal degeneration; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0008764; MedGen: C2931258; Orphanet: 65; OMIM: 204000

Recent activity

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PREDICTED: Brassica napus NAC domain-containing protein 6 (LOC111204246), mRNA
PREDICTED: Brassica napus NAC domain-containing protein 6 (LOC111204246), mRNA
gi|2258270806|ref|XM_022698533.2|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001220657	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Feb 29, 2020)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 10951519, 11328726, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001220657

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Feb 29, 2020)

germline

clinical testing

PubMed (3)
[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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Spectrum of retGC1 mutations in Leber's congenital amaurosis.

Perrault I, Rozet JM, Gerber S, Ghazi I, Ducroq D, Souied E, Leowski C, Bonnemaison M, Dufier JL, Munnich A, Kaplan J.

Eur J Hum Genet. 2000 Aug;8(8):578-82.

PubMed [citation]

PMID:: 10951519

Complete abolition of the retinal-specific guanylyl cyclase (retGC-1) catalytic ability consistently leads to leber congenital amaurosis (LCA).

Rozet JM, Perrault I, Gerber S, Hanein S, Barbet F, Ducroq D, Souied E, Munnich A, Kaplan J.

Invest Ophthalmol Vis Sci. 2001 May;42(6):1190-2.

PubMed [citation]

PMID:: 11328726

See all PubMed Citations (3)

Details of each submission

From Invitae, SCV001220657.5

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

Description

For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in GUCY2D are known to be pathogenic (PMID: 10951519, 11328726). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has not been reported in the literature in individuals with GUCY2D-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Tyr996*) in the GUCY2D gene. It is expected to result in an absent or disrupted protein product.

#	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: Apr 6, 2024

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