17-8014859-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_000180.4(GUCY2D):​c.2577G>T​(p.Pro859=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00382 in 1,614,102 control chromosomes in the GnomAD database, including 141 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0059 ( 14 hom., cov: 32)
Exomes 𝑓: 0.0036 ( 127 hom. )

Consequence

GUCY2D
NM_000180.4 splice_region, synonymous

Scores

2
Splicing: ADA: 0.7349
1
1

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.332
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]

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=-0.51).
BP6
Variant 17-8014859-G-T is Benign according to our data. Variant chr17-8014859-G-T is described in ClinVar as [Benign]. Clinvar id is 194323.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00587 (893/152250) while in subpopulation SAS AF= 0.0485 (234/4820). AF 95% confidence interval is 0.0434. There are 14 homozygotes in gnomad4. There are 468 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 14 AD,AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GUCY2DNM_000180.4 linkuse as main transcriptc.2577G>T p.Pro859= splice_region_variant, synonymous_variant 14/20 ENST00000254854.5
GUCY2DXM_011523816.2 linkuse as main transcriptc.2577G>T p.Pro859= splice_region_variant, synonymous_variant 13/19

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GUCY2DENST00000254854.5 linkuse as main transcriptc.2577G>T p.Pro859= splice_region_variant, synonymous_variant 14/201 NM_000180.4 P1
ENST00000623126.1 linkuse as main transcriptn.1520C>A non_coding_transcript_exon_variant 1/1

Frequencies

GnomAD3 genomes
AF:
0.00581
AC:
884
AN:
152132
Hom.:
13
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0139
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000981
Gnomad ASJ
AF:
0.00230
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.0481
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000588
Gnomad OTH
AF:
0.00574
GnomAD3 exomes
AF:
0.00679
AC:
1707
AN:
251356
Hom.:
45
AF XY:
0.00834
AC XY:
1133
AN XY:
135872
show subpopulations
Gnomad AFR exome
AF:
0.0146
Gnomad AMR exome
AF:
0.000810
Gnomad ASJ exome
AF:
0.00268
Gnomad EAS exome
AF:
0.000163
Gnomad SAS exome
AF:
0.0428
Gnomad FIN exome
AF:
0.0000462
Gnomad NFE exome
AF:
0.000634
Gnomad OTH exome
AF:
0.00472
GnomAD4 exome
AF:
0.00360
AC:
5265
AN:
1461852
Hom.:
127
Cov.:
35
AF XY:
0.00470
AC XY:
3420
AN XY:
727228
show subpopulations
Gnomad4 AFR exome
AF:
0.0155
Gnomad4 AMR exome
AF:
0.00105
Gnomad4 ASJ exome
AF:
0.00295
Gnomad4 EAS exome
AF:
0.000126
Gnomad4 SAS exome
AF:
0.0422
Gnomad4 FIN exome
AF:
0.0000374
Gnomad4 NFE exome
AF:
0.000587
Gnomad4 OTH exome
AF:
0.00517
GnomAD4 genome
AF:
0.00587
AC:
893
AN:
152250
Hom.:
14
Cov.:
32
AF XY:
0.00629
AC XY:
468
AN XY:
74446
show subpopulations
Gnomad4 AFR
AF:
0.0140
Gnomad4 AMR
AF:
0.000980
Gnomad4 ASJ
AF:
0.00230
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.0485
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000588
Gnomad4 OTH
AF:
0.00616
Alfa
AF:
0.00140
Hom.:
0
Bravo
AF:
0.00516
Asia WGS
AF:
0.0310
AC:
109
AN:
3478
EpiCase
AF:
0.000981
EpiControl
AF:
0.000652

ClinVar

Significance: Benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:3
Benign, criteria provided, single submitterclinical testingARUP Laboratories, Molecular Genetics and Genomics, ARUP LaboratoriesApr 28, 2017- -
Benign, criteria provided, single submitterclinical testingEurofins Ntd Llc (ga)May 13, 2015- -
Benign, criteria provided, single submitterclinical testingLaboratory for Molecular Medicine, Mass General Brigham Personalized MedicineMar 28, 2016Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -
Cone-rod dystrophy 6;C2931258:Leber congenital amaurosis 1 Benign:1
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 31, 2024- -
not provided Benign:1
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.51
CADD
Benign
13
DANN
Benign
0.64

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.73
dbscSNV1_RF
Pathogenic
0.82
SpliceAI score (max)
0.030
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.

Other links and lift over

dbSNP: rs112372281; hg19: chr17-7918177; API