NM_000180.4(GUCY2D):c.1582C>T (p.Arg528Ter) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 8, 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:: RCV001235694.7

Allele description [Variation Report for NM_000180.4(GUCY2D):c.1582C>T (p.Arg528Ter)]

NM_000180.4(GUCY2D):c.1582C>T (p.Arg528Ter)

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.1582C>T (p.Arg528Ter)

HGVS:

NC_000017.11:g.8007946C>T
NG_009092.1:g.10277C>T
NM_000180.4:c.1582C>TMANE SELECT
NP_000171.1:p.Arg528Ter
NC_000017.10:g.7911264C>T
NM_000180.3:c.1582C>T

Protein change:

R528*

Links:

dbSNP: rs1349155167

NCBI 1000 Genomes Browser:

rs1349155167

Molecular consequence:

NM_000180.4:c.1582C>T - 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; RETINAL BLINDNESS, CONGENITAL; Congenital absence of the rods and cones; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0008764; MedGen: C2931258; Orphanet: 65; OMIM: 204000

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001408393	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 8, 2022)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 31630094, 34048777, 10951519, 11328726, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001408393

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 8, 2022)

germline

clinical testing

PubMed (5)
[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

Genetic and clinical findings in a Chinese cohort with Leber congenital amaurosis and early onset severe retinal dystrophy.

Xu K, Xie Y, Sun T, Zhang X, Chen C, Li Y.

Br J Ophthalmol. 2020 Jul;104(7):932-937. doi: 10.1136/bjophthalmol-2019-314281. Epub 2019 Oct 19.

PubMed [citation]

PMID:: 31630094

Novel variants in GUCY2D causing retinopathy and the genotype-phenotype correlation.

Yi Z, Sun W, Xiao X, Li S, Jia X, Li X, Yu B, Wang P, Zhang Q.

Exp Eye Res. 2021 Jul;208:108637. doi: 10.1016/j.exer.2021.108637. Epub 2021 May 26.

PubMed [citation]

PMID:: 34048777

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001408393.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This premature translational stop signal has been observed in individual(s) with clinical features of GUCY2D-related conditions (PMID: 31630094, 34048777). This sequence change creates a premature translational stop signal (p.Arg528*) in the GUCY2D gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in GUCY2D are known to be pathogenic (PMID: 10951519, 11328726). 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. ClinVar contains an entry for this variant (Variation ID: 961926). For these reasons, this variant has been classified as Pathogenic.

#	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: Mar 5, 2025

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