NM_000180.4(GUCY2D):c.1978C>T (p.Arg660Ter) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 8, 2023
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:: RCV001047937.8

Allele description [Variation Report for NM_000180.4(GUCY2D):c.1978C>T (p.Arg660Ter)]

NM_000180.4(GUCY2D):c.1978C>T (p.Arg660Ter)

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.1978C>T (p.Arg660Ter)

HGVS:

NC_000017.11:g.8012471C>T
NG_009092.1:g.14802C>T
NM_000180.4:c.1978C>TMANE SELECT
NP_000171.1:p.Arg660Ter
NP_000171.1:p.Arg660Ter
NC_000017.10:g.7915789C>T
NM_000180.3:c.1978C>T

Protein change:

R660*

Links:

dbSNP: rs61750161

NCBI 1000 Genomes Browser:

rs61750161

Molecular consequence:

NM_000180.4:c.1978C>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; 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

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001211922	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 8, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 10951519, 11328726, 24997176, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001211922

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 8, 2023)

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	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 (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001211922.5

#	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 creates a premature translational stop signal (p.Arg660*) 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). This variant is present in population databases (rs61750161, gnomAD 0.0009%). This premature translational stop signal has been observed in individuals with Leber congenital amaurosis (PMID: 24997176). ClinVar contains an entry for this variant (Variation ID: 98554). 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: Nov 3, 2024

ClinVar

Relating variation to medicine