rs3829789

Variant names:

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.741C>T(p.His247His) 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:5

Conservation

PhyloP100: 0.400

Publications

13 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: G2P, Orphanet
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 17-8003871-C-T is Benign according to our data. Variant chr17-8003871-C-T is described in ClinVar as Benign. ClinVar VariationId is 92582.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000180.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GUCY2D	NM_000180.4	MANE Select	c.741C>T	p.His247His	synonymous	Exon 3 of 20	NP_000171.1	Q02846

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GUCY2D	ENST00000254854.5	TSL:1 MANE Select	c.741C>T	p.His247His	synonymous	Exon 3 of 20	ENSP00000254854.4	Q02846

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

GnomAD2 exomes

AF:

0.118

AC:

29372

AN:

248952

AF XY:

0.118

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 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

African (AFR)

AF:

0.0741

AC:

2480

AN:

33470

American (AMR)

AF:

0.0920

AC:

4111

AN:

44692

Ashkenazi Jewish (ASJ)

AF:

0.0620

AC:

1617

AN:

26098

East Asian (EAS)

AF:

0.195

AC:

7732

AN:

39690

South Asian (SAS)

AF:

0.119

AC:

10222

AN:

86232

European-Finnish (FIN)

AF:

0.116

AC:

6078

AN:

52490

Middle Eastern (MID)

AF:

0.0775

AC:

447

AN:

5766

European-Non Finnish (NFE)

AF:

0.133

AC:

147415

AN:

1111720

Other (OTH)

AF:

0.125

AC:

7565

AN:

60368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

9995

19991

29986

39982

49977

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5382

10764

16146

21528

26910

<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:

16555

AN:

152242

Hom.:

999

Cov.:

AF XY:

0.109

AC XY:

8147

AN XY:

74436

show subpopulations

African (AFR)

AF:

0.0726

AC:

3017

AN:

41564

American (AMR)

AF:

0.100

AC:

1532

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0602

AC:

209

AN:

3472

East Asian (EAS)

AF:

0.216

AC:

1118

AN:

5164

South Asian (SAS)

AF:

0.115

AC:

558

AN:

4832

European-Finnish (FIN)

AF:

0.110

AC:

1167

AN:

10600

Middle Eastern (MID)

AF:

0.116

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.128

AC:

8672

AN:

67996

Other (OTH)

AF:

0.0967

AC:

204

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

771

1542

2313

3084

3855

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

198

396

594

792

990

<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:

0.113

Hom.:

526

Bravo

AF:

0.107

Asia WGS

AF:

0.164

AC:

570

AN:

3478

EpiCase

AF:

0.114

EpiControl

AF:

0.112

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (2)

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

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.41

CADD

Benign

7.3

(source)

DANN

Benign

0.95

PhyloP100

0.40

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over