rs56130505

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000180.4(GUCY2D):c.2109G>A(p.Ala703Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0956 in 1,611,898 control chromosomes in the GnomAD database, including 8,406 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 1137 hom., cov: 32)

Exomes 𝑓: 0.094 ( 7269 hom. )

Consequence

GUCY2D
NM_000180.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4O:1

Conservation

PhyloP100: -6.01

Publications

3 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 17-8012602-G-A is Benign according to our data. Variant chr17-8012602-G-A is described in ClinVar as Benign. ClinVar VariationId is 98559.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-6.01 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GUCY2D	NM_000180.4 link	c.2109G>A	p.Ala703Ala	synonymous_variant	Exon 10 of 20	ENST00000254854.5	NP_000171.1
GUCY2D	XM_011523816.2 link	c.2109G>A	p.Ala703Ala	synonymous_variant	Exon 9 of 19		XP_011522118.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GUCY2D	ENST00000254854.5 link	c.2109G>A	p.Ala703Ala	synonymous_variant	Exon 10 of 20	1	NM_000180.4	ENSP00000254854.4

Frequencies

GnomAD3 genomes

AF:

0.109

AC:

16571

AN:

152044

Hom.:

1133

Cov.:

show subpopulations

Gnomad AFR

AF:

0.187

Gnomad AMI

AF:

0.0471

Gnomad AMR

AF:

0.0508

Gnomad ASJ

AF:

0.0669

Gnomad EAS

AF:

0.000580

Gnomad SAS

AF:

0.0394

Gnomad FIN

AF:

0.0682

Gnomad MID

AF:

0.0728

Gnomad NFE

AF:

0.0981

Gnomad OTH

AF:

0.0813

GnomAD2 exomes

AF:

0.0757

AC:

18736

AN:

247652

AF XY:

0.0739

show subpopulations

Gnomad AFR exome

AF:

0.186

Gnomad AMR exome

AF:

0.0349

Gnomad ASJ exome

AF:

0.0617

Gnomad EAS exome

AF:

0.000437

Gnomad FIN exome

AF:

0.0782

Gnomad NFE exome

AF:

0.0955

Gnomad OTH exome

AF:

0.0688

GnomAD4 exome

AF:

0.0942

AC:

137548

AN:

1459736

Hom.:

7269

Cov.:

AF XY:

0.0926

AC XY:

67258

AN XY:

726172

show subpopulations

African (AFR)

AF:

0.194

AC:

6494

AN:

33432

American (AMR)

AF:

0.0365

AC:

1633

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.0618

AC:

1614

AN:

26128

East Asian (EAS)

AF:

0.000252

AC:

AN:

39694

South Asian (SAS)

AF:

0.0419

AC:

3613

AN:

86234

European-Finnish (FIN)

AF:

0.0781

AC:

4110

AN:

52658

Middle Eastern (MID)

AF:

0.0470

AC:

271

AN:

5764

European-Non Finnish (NFE)

AF:

0.103

AC:

114511

AN:

1110748

Other (OTH)

AF:

0.0877

AC:

5292

AN:

60356

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

6168

12336

18503

24671

30839

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4190

8380

12570

16760

20950

<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:

0.109

AC:

16596

AN:

152162

Hom.:

1137

Cov.:

AF XY:

0.105

AC XY:

7788

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.187

AC:

7768

AN:

41494

American (AMR)

AF:

0.0506

AC:

773

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.0669

AC:

232

AN:

3468

East Asian (EAS)

AF:

0.000581

AC:

AN:

5160

South Asian (SAS)

AF:

0.0394

AC:

190

AN:

4820

European-Finnish (FIN)

AF:

0.0682

AC:

723

AN:

10604

Middle Eastern (MID)

AF:

0.0748

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0981

AC:

6672

AN:

68012

Other (OTH)

AF:

0.0804

AC:

170

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

749

1498

2247

2996

3745

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

176

352

528

704

880

<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:

0.0971

Hom.:

679

Bravo

AF:

0.111

Asia WGS

AF:

0.0250

AC:

AN:

3478

EpiCase

AF:

0.0881

EpiControl

AF:

0.0858

ClinVar

Significance: Benign

Submissions summary: Benign:4Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2Other:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Apr 26, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

Retina International

Significance:not provided

Review Status:no classification provided

Collection Method:literature only

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

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

-0.88

CADD

Benign

0.29

(source)

DANN

Benign

0.62

PhyloP100

-6.0

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

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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