Variant rs56034424 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.1119G>A(p.Val373=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0206 in 1,605,346 control chromosomes in the GnomAD database, including 460 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.019 ( 35 hom., cov: 32)

Exomes 𝑓: 0.021 ( 425 hom. )

Consequence

GUCY2D
NM_000180.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.76

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 17-8006455-G-A is Benign according to our data. Variant chr17-8006455-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 471237.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-8006455-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=1.76 with no splicing effect.

BA1

GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0526 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.1119G>A	p.Val373=	synonymous_variant	4/20	ENST00000254854.5	NP_000171.1
GUCY2D	XM_011523816.2 linkuse as main transcript	c.1119G>A	p.Val373=	synonymous_variant	3/19		XP_011522118.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GUCY2D	ENST00000254854.5 linkuse as main transcript	c.1119G>A	p.Val373=	synonymous_variant	4/20	1	NM_000180.4	ENSP00000254854	P1

Frequencies

GnomAD3 genomes

AF:

0.0190

AC:

2888

AN:

152248

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00432

Gnomad AMI

AF:

0.0285

Gnomad AMR

AF:

0.0236

Gnomad ASJ

AF:

0.0593

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00269

Gnomad FIN

AF:

0.0452

Gnomad MID

AF:

0.0633

Gnomad NFE

AF:

0.0226

Gnomad OTH

AF:

0.0306

GnomAD3 exomes

AF:

0.0197

AC:

4800

AN:

243046

Hom.:

AF XY:

0.0202

AC XY:

2669

AN XY:

132254

show subpopulations

Gnomad AFR exome

AF:

0.00382

Gnomad AMR exome

AF:

0.0129

Gnomad ASJ exome

AF:

0.0599

Gnomad EAS exome

AF:

0.0000547

Gnomad SAS exome

AF:

0.00419

Gnomad FIN exome

AF:

0.0402

Gnomad NFE exome

AF:

0.0246

Gnomad OTH exome

AF:

0.0312

GnomAD4 exome

AF:

0.0208

AC:

30168

AN:

1452980

Hom.:

425

Cov.:

AF XY:

0.0207

AC XY:

14942

AN XY:

723230

show subpopulations

Gnomad4 AFR exome

AF:

0.00284

Gnomad4 AMR exome

AF:

0.0146

Gnomad4 ASJ exome

AF:

0.0569

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00446

Gnomad4 FIN exome

AF:

0.0424

Gnomad4 NFE exome

AF:

0.0215

Gnomad4 OTH exome

AF:

0.0237

GnomAD4 genome

AF:

0.0190

AC:

2888

AN:

152366

Hom.:

Cov.:

AF XY:

0.0198

AC XY:

1472

AN XY:

74516

show subpopulations

Gnomad4 AFR

AF:

0.00430

Gnomad4 AMR

AF:

0.0236

Gnomad4 ASJ

AF:

0.0593

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00269

Gnomad4 FIN

AF:

0.0452

Gnomad4 NFE

AF:

0.0226

Gnomad4 OTH

AF:

0.0303

Alfa

AF:

0.0250

Hom.:

Bravo

AF:

0.0170

Asia WGS

AF:

0.00346

AC:

AN:

3478

EpiCase

AF:

0.0288

EpiControl

AF:

0.0286

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

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	- -

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

-0.41

CADD

Benign

5.1

DANN

Benign

0.63

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