NM_000180.4(GUCY2D):c.690_693del (p.Lys232fs) 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:: RCV001866149.5

Allele description [Variation Report for NM_000180.4(GUCY2D):c.690_693del (p.Lys232fs)]

NM_000180.4(GUCY2D):c.690_693del (p.Lys232fs)

Gene:

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

Variant type:

Deletion

Cytogenetic location:

17p13.1

Genomic location:

Preferred name:

NM_000180.4(GUCY2D):c.690_693del (p.Lys232fs)

HGVS:

NC_000017.11:g.8003737_8003740del
NG_009092.1:g.6068_6071del
NM_000180.4:c.690_693delMANE SELECT
NP_000171.1:p.Lys232fs
NC_000017.10:g.7907055_7907058del

Protein change:

K232fs

Links:

dbSNP: rs2151799567

NCBI 1000 Genomes Browser:

rs2151799567

Molecular consequence:

NM_000180.4:c.690_693del - frameshift variant - [Sequence Ontology: SO:0001589]

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
SCV002232225	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 8, 2022)	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

SCV002232225

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 8, 2022)

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV002232225.4

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

Description

ClinVar contains an entry for this variant (Variation ID: 1213844). This variant has not been reported in the literature in individuals affected with GUCY2D-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Lys232Phefs*10) 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). For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site.

#	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 13, 2025

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