rs56034424

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_000180.4(GUCY2D):c.1119G>A(p.Val373Val) 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

Publications

5 publications found

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 Gene-Disease associations (from GenCC):

cone-rod dystrophy
Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, G2P
GUCY2D-related dominant retinopathy
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
GUCY2D-related recessive retinopathy
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
Leber congenital amaurosis 1
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
cone-rod dystrophy 6
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
night blindness, congenital stationary, type1i
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
Leber congenital amaurosis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
central areolar choroidal dystrophy
Inheritance: AR, AD Classification: SUPPORTIVE, LIMITED Submitted by: G2P, Orphanet

GUCY2D links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 Benign/Likely_benign. ClinVar VariationId is 471237.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 rank	MANE	Protein	UniProt
GUCY2D	NM_000180.4 link	c.1119G>A	p.Val373Val	synonymous_variant	Exon 4 of 20	ENST00000254854.5	NP_000171.1
GUCY2D	XM_011523816.2 link	c.1119G>A	p.Val373Val	synonymous_variant	Exon 3 of 19		XP_011522118.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GUCY2D	ENST00000254854.5 link	c.1119G>A	p.Val373Val	synonymous_variant	Exon 4 of 20	1	NM_000180.4	ENSP00000254854.4

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

GnomAD2 exomes

AF:

0.0197

AC:

4800

AN:

243046

AF XY:

0.0202

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 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

African (AFR)

AF:

0.00284

AC:

AN:

33478

American (AMR)

AF:

0.0146

AC:

651

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.0569

AC:

1487

AN:

26118

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39698

South Asian (SAS)

AF:

0.00446

AC:

385

AN:

86250

European-Finnish (FIN)

AF:

0.0424

AC:

1893

AN:

44690

Middle Eastern (MID)

AF:

0.0577

AC:

333

AN:

5768

European-Non Finnish (NFE)

AF:

0.0215

AC:

23896

AN:

1111926

Other (OTH)

AF:

0.0237

AC:

1427

AN:

60336

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

1846

3693

5539

7386

9232

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

846

1692

2538

3384

4230

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0190

AC:

2888

AN:

152366

Hom.:

Cov.:

AF XY:

0.0198

AC XY:

1472

AN XY:

74516

show subpopulations

African (AFR)

AF:

0.00430

AC:

179

AN:

41590

American (AMR)

AF:

0.0236

AC:

361

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0593

AC:

206

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00269

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.0452

AC:

480

AN:

10626

Middle Eastern (MID)

AF:

0.0680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0226

AC:

1539

AN:

68034

Other (OTH)

AF:

0.0303

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

150

300

449

599

749

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

150

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

May 23, 2021

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Nov 29, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.41

CADD

Benign

5.1

(source)

DANN

Benign

0.63

PhyloP100

1.8

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over