Variant chr17-8012602-G-A 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.2109G>A(p.Ala703=) 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

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 98559.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-8012602-G-A is described in Lovd as [Benign].

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/exons	MANE	UniProt
GUCY2D	NM_000180.4 linkuse as main transcript	c.2109G>A	p.Ala703=	synonymous_variant	10/20	ENST00000254854.5
GUCY2D	XM_011523816.2 linkuse as main transcript	c.2109G>A	p.Ala703=	synonymous_variant	9/19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GUCY2D	ENST00000254854.5 linkuse as main transcript	c.2109G>A	p.Ala703=	synonymous_variant	10/20	1	NM_000180.4	P1

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

GnomAD3 exomes

AF:

0.0757

AC:

18736

AN:

247652

Hom.:

985

AF XY:

0.0739

AC XY:

9923

AN XY:

134298

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 SAS exome

AF:

0.0412

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

Gnomad4 AFR exome

AF:

0.194

Gnomad4 AMR exome

AF:

0.0365

Gnomad4 ASJ exome

AF:

0.0618

Gnomad4 EAS exome

AF:

0.000252

Gnomad4 SAS exome

AF:

0.0419

Gnomad4 FIN exome

AF:

0.0781

Gnomad4 NFE exome

AF:

0.103

Gnomad4 OTH exome

AF:

0.0877

GnomAD4 genome

AF:

0.109

AC:

16596

AN:

152162

Hom.:

1137

Cov.:

AF XY:

0.105

AC XY:

7788

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.187

Gnomad4 AMR

AF:

0.0506

Gnomad4 ASJ

AF:

0.0669

Gnomad4 EAS

AF:

0.000581

Gnomad4 SAS

AF:

0.0394

Gnomad4 FIN

AF:

0.0682

Gnomad4 NFE

AF:

0.0981

Gnomad4 OTH

AF:

0.0804

Alfa

AF:

0.0960

Hom.:

385

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

not provided, no classification provided	literature only	Retina International	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 26, 2018	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. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

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

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.29

DANN

Benign

0.62

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