Variant rs3829789 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_000180.4(GUCY2D):c.741C>T(p.His247=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 1,612,768 control chromosomes in the GnomAD database, including 13,568 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 999 hom., cov: 32)

Exomes 𝑓: 0.13 ( 12569 hom. )

Consequence

GUCY2D
NM_000180.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.400

Variant links:

Genes affected

GUCY2D (HGNC:4689): (guanylate cyclase 2D, retinal) This gene encodes a retina-specific guanylate cyclase, which is a member of the membrane guanylyl cyclase family. Like other membrane guanylyl cyclases, this enzyme has a hydrophobic amino-terminal signal sequence followed by a large extracellular domain, a single membrane spanning domain, a kinase homology domain, and a guanylyl cyclase catalytic domain. In contrast to other membrane guanylyl cyclases, this enzyme is not activated by natriuretic peptides. Mutations in this gene result in Leber congenital amaurosis and cone-rod dystrophy-6 diseases. [provided by RefSeq, Dec 2008]

GUCY2D links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.41).

BP6

Variant 17-8003871-C-T is Benign according to our data. Variant chr17-8003871-C-T is described in ClinVar as [Benign]. Clinvar id is 92582.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-8003871-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.4 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.206 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GUCY2D	NM_000180.4 linkuse as main transcript	c.741C>T	p.His247=	synonymous_variant	3/20	ENST00000254854.5
GUCY2D	XM_011523816.2 linkuse as main transcript	c.741C>T	p.His247=	synonymous_variant	2/19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GUCY2D	ENST00000254854.5 linkuse as main transcript	c.741C>T	p.His247=	synonymous_variant	3/20	1	NM_000180.4	P1

Frequencies

GnomAD3 genomes

AF:

0.109

AC:

16549

AN:

152124

Hom.:

999

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0725

Gnomad AMI

AF:

0.0484

Gnomad AMR

AF:

0.100

Gnomad ASJ

AF:

0.0602

Gnomad EAS

AF:

0.217

Gnomad SAS

AF:

0.115

Gnomad FIN

AF:

0.110

Gnomad MID

AF:

0.117

Gnomad NFE

AF:

0.128

Gnomad OTH

AF:

0.0967

GnomAD3 exomes

AF:

0.118

AC:

29372

AN:

248952

Hom.:

1874

AF XY:

0.118

AC XY:

15988

AN XY:

135010

show subpopulations

Gnomad AFR exome

AF:

0.0749

Gnomad AMR exome

AF:

0.0930

Gnomad ASJ exome

AF:

0.0632

Gnomad EAS exome

AF:

0.208

Gnomad SAS exome

AF:

0.115

Gnomad FIN exome

AF:

0.118

Gnomad NFE exome

AF:

0.124

Gnomad OTH exome

AF:

0.105

GnomAD4 exome

AF:

0.128

AC:

187667

AN:

1460526

Hom.:

12569

Cov.:

AF XY:

0.128

AC XY:

93245

AN XY:

726628

show subpopulations

Gnomad4 AFR exome

AF:

0.0741

Gnomad4 AMR exome

AF:

0.0920

Gnomad4 ASJ exome

AF:

0.0620

Gnomad4 EAS exome

AF:

0.195

Gnomad4 SAS exome

AF:

0.119

Gnomad4 FIN exome

AF:

0.116

Gnomad4 NFE exome

AF:

0.133

Gnomad4 OTH exome

AF:

0.125

GnomAD4 genome

AF:

0.109

AC:

16555

AN:

152242

Hom.:

999

Cov.:

AF XY:

0.109

AC XY:

8147

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.0726

Gnomad4 AMR

AF:

0.100

Gnomad4 ASJ

AF:

0.0602

Gnomad4 EAS

AF:

0.216

Gnomad4 SAS

AF:

0.115

Gnomad4 FIN

AF:

0.110

Gnomad4 NFE

AF:

0.128

Gnomad4 OTH

AF:

0.0967

Alfa

AF:

0.113

Hom.:

526

Bravo

AF:

0.107

Asia WGS

AF:

0.164

AC:

570

AN:

3478

EpiCase

AF:

0.114

EpiControl

AF:

0.112

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Aug 08, 2013	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Cone-rod dystrophy 6;C2931258:Leber congenital amaurosis 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 26, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.41

CADD

Benign

7.3

DANN

Benign

0.95

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over