NM_000180.4(GUCY2D):c.3038G>A (p.Gly1013Glu) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Feb 3, 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:: RCV003770363.2

Allele description [Variation Report for NM_000180.4(GUCY2D):c.3038G>A (p.Gly1013Glu)]

NM_000180.4(GUCY2D):c.3038G>A (p.Gly1013Glu)

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.3038G>A (p.Gly1013Glu)

HGVS:

NC_000017.11:g.8015836G>A
NG_009092.1:g.18167G>A
NM_000180.4:c.3038G>AMANE SELECT
NP_000171.1:p.Gly1013Glu
NC_000017.10:g.7919154G>A
NM_000180.3:c.3038G>A

Protein change:

G1013E

Links:

dbSNP: rs1975959442

NCBI 1000 Genomes Browser:

rs1975959442

Molecular consequence:

NM_000180.4:c.3038G>A - missense variant - [Sequence Ontology: SO:0001583]

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004571013	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Feb 3, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 26047050, 28966547, 32165824, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004571013

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Feb 3, 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

Comprehensive Molecular Diagnosis of a Large Chinese Leber Congenital Amaurosis Cohort.

Wang H, Wang X, Zou X, Xu S, Li H, Soens ZT, Wang K, Li Y, Dong F, Chen R, Sui R.

Invest Ophthalmol Vis Sci. 2015 Jun;56(6):3642-55. doi: 10.1167/iovs.14-15972.

PubMed [citation]

PMID:: 26047050
PMCID:: PMC4466882

Diagnostic application of clinical exome sequencing in Leber congenital amaurosis.

Han J, Rim JH, Hwang IS, Kim J, Shin S, Lee ST, Choi JR.

Mol Vis. 2017;23:649-659.

PubMed [citation]

PMID:: 28966547
PMCID:: PMC5610811

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004571013.1

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

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Gly1013 amino acid residue in GUCY2D. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 26047050; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 982538). This missense change has been observed in individual(s) with Leber congenital amaurosis (PMID: 28966547, 32165824). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 1013 of the GUCY2D protein (p.Gly1013Glu).

#	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

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