Variant chr17-8015861-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000180.4(GUCY2D):c.3043+20G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0191 in 1,607,184 control chromosomes in the GnomAD database, including 560 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.017 ( 55 hom., cov: 33)

Exomes 𝑓: 0.019 ( 505 hom. )

Consequence

GUCY2D
NM_000180.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.508

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:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 17-8015861-G-C is Benign according to our data. Variant chr17-8015861-G-C is described in ClinVar as [Benign]. Clinvar id is 255477.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.06 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.3043+20G>C		intron_variant		ENST00000254854.5	NP_000171.1
GUCY2D	XM_011523816.2 linkuse as main transcript	c.3043+20G>C		intron_variant			XP_011522118.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GUCY2D	ENST00000254854.5 linkuse as main transcript	c.3043+20G>C		intron_variant		1	NM_000180.4	ENSP00000254854	P1
	ENST00000623126.1 linkuse as main transcript	n.518C>G		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes

AF:

0.0173

AC:

2627

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00444

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.0391

Gnomad ASJ

AF:

0.00403

Gnomad EAS

AF:

0.0309

Gnomad SAS

AF:

0.0655

Gnomad FIN

AF:

0.0213

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0159

Gnomad OTH

AF:

0.0182

GnomAD3 exomes

AF:

0.0239

AC:

5729

AN:

239250

Hom.:

135

AF XY:

0.0257

AC XY:

3345

AN XY:

129994

show subpopulations

Gnomad AFR exome

AF:

0.00406

Gnomad AMR exome

AF:

0.0293

Gnomad ASJ exome

AF:

0.00275

Gnomad EAS exome

AF:

0.0263

Gnomad SAS exome

AF:

0.0668

Gnomad FIN exome

AF:

0.0194

Gnomad NFE exome

AF:

0.0159

Gnomad OTH exome

AF:

0.0212

GnomAD4 exome

AF:

0.0193

AC:

28077

AN:

1454858

Hom.:

505

Cov.:

AF XY:

0.0207

AC XY:

14951

AN XY:

723572

show subpopulations

Gnomad4 AFR exome

AF:

0.00279

Gnomad4 AMR exome

AF:

0.0301

Gnomad4 ASJ exome

AF:

0.00227

Gnomad4 EAS exome

AF:

0.0126

Gnomad4 SAS exome

AF:

0.0671

Gnomad4 FIN exome

AF:

0.0189

Gnomad4 NFE exome

AF:

0.0162

Gnomad4 OTH exome

AF:

0.0223

GnomAD4 genome

AF:

0.0173

AC:

2630

AN:

152326

Hom.:

Cov.:

AF XY:

0.0189

AC XY:

1404

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.00442

Gnomad4 AMR

AF:

0.0393

Gnomad4 ASJ

AF:

0.00403

Gnomad4 EAS

AF:

0.0306

Gnomad4 SAS

AF:

0.0660

Gnomad4 FIN

AF:

0.0213

Gnomad4 NFE

AF:

0.0160

Gnomad4 OTH

AF:

0.0184

Alfa

AF:

0.00821

Hom.:

Bravo

AF:

0.0148

Asia WGS

AF:

0.0570

AC:

199

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 08, 2019	- -

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

-0.80

CADD

Benign

7.2

DANN

Benign

0.67

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