Variant rs142351773 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000180.4(GUCY2D):c.3297G>A(p.Pro1099Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0207 in 1,568,828 control chromosomes in the GnomAD database, including 439 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.020 ( 34 hom., cov: 33)

Exomes 𝑓: 0.021 ( 405 hom. )

Consequence

GUCY2D
NM_000180.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -5.26

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:

GUCY2D (HGNC:):

GUCY2D links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 17-8016515-G-A is Benign according to our data. Variant chr17-8016515-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 194916.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-5.26 with no splicing effect.

BA1

GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0508 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GUCY2D	NM_000180.4 linkuse as main transcript	c.3297G>A	p.Pro1099Pro	synonymous_variant	19/20	ENST00000254854.5	NP_000171.1	Q02846
GUCY2D	XM_011523816.2 linkuse as main transcript	c.3297G>A	p.Pro1099Pro	synonymous_variant	18/19		XP_011522118.1	Q02846

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GUCY2D	ENST00000254854.5 linkuse as main transcript	c.3297G>A	p.Pro1099Pro	synonymous_variant	19/20	1	NM_000180.4	ENSP00000254854.4		Q02846
GUCY2D	ENST00000574510.1 linkuse as main transcript	n.235G>A		non_coding_transcript_exon_variant	2/2	4

Frequencies

GnomAD3 genomes

AF:

0.0198

AC:

3014

AN:

152110

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00755

Gnomad AMI

AF:

0.0286

Gnomad AMR

AF:

0.0238

Gnomad ASJ

AF:

0.0594

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00456

Gnomad FIN

AF:

0.0447

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.0224

Gnomad OTH

AF:

0.0310

GnomAD3 exomes

AF:

0.0217

AC:

3724

AN:

171582

Hom.:

AF XY:

0.0215

AC XY:

2012

AN XY:

93406

show subpopulations

Gnomad AFR exome

AF:

0.00894

Gnomad AMR exome

AF:

0.0145

Gnomad ASJ exome

AF:

0.0609

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00495

Gnomad FIN exome

AF:

0.0491

Gnomad NFE exome

AF:

0.0253

Gnomad OTH exome

AF:

0.0331

GnomAD4 exome

AF:

0.0208

AC:

29420

AN:

1416600

Hom.:

405

Cov.:

AF XY:

0.0206

AC XY:

14455

AN XY:

701048

show subpopulations

Gnomad4 AFR exome

AF:

0.00641

Gnomad4 AMR exome

AF:

0.0158

Gnomad4 ASJ exome

AF:

0.0568

Gnomad4 EAS exome

AF:

0.000106

Gnomad4 SAS exome

AF:

0.00493

Gnomad4 FIN exome

AF:

0.0446

Gnomad4 NFE exome

AF:

0.0211

Gnomad4 OTH exome

AF:

0.0236

GnomAD4 genome

AF:

0.0198

AC:

3012

AN:

152228

Hom.:

Cov.:

AF XY:

0.0207

AC XY:

1538

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.00753

Gnomad4 AMR

AF:

0.0238

Gnomad4 ASJ

AF:

0.0594

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00436

Gnomad4 FIN

AF:

0.0447

Gnomad4 NFE

AF:

0.0224

Gnomad4 OTH

AF:

0.0307

Alfa

AF:

0.0241

Hom.:

Bravo

AF:

0.0177

Asia WGS

AF:

0.00520

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	May 23, 2021	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 29, 2023	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Sep 03, 2014

- -

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

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.010

DANN

Benign

0.78

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