Variant 17-81650590-A-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_002602.4(PDE6G):c.*484T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.043 in 454,244 control chromosomes in the GnomAD database, including 773 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.043 ( 252 hom., cov: 32)

Exomes 𝑓: 0.043 ( 521 hom. )

Consequence

PDE6G
NM_002602.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.865

Variant links:

Genes affected

PDE6G (HGNC:8789): (phosphodiesterase 6G) This gene encodes the gamma subunit of cyclic GMP-phosphodiesterase, which is composed of alpha- and beta- catalytic subunits and two identical, inhibitory gamma subunits. This gene is expressed in rod photoreceptors and functions in the phototransduction signaling cascade. It is also expressed in a variety of other tissues, and has been shown to regulate the c-Src protein kinase and G-protein-coupled receptor kinase 2. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2009]

PDE6G links:

PDE6G (HGNC:):

PDE6G 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=-0.92).

BP6

Variant 17-81650590-A-C is Benign according to our data. Variant chr17-81650590-A-C is described in ClinVar as [Benign]. Clinvar id is 325852.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.201 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDE6G	NM_002602.4 linkuse as main transcript	c.*484T>G		3_prime_UTR_variant	4/4	ENST00000331056.10	NP_002593.1	P18545

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDE6G	ENST00000331056.10 linkuse as main transcript	c.*484T>G		3_prime_UTR_variant	4/4	1	NM_002602.4	ENSP00000328412.5		P18545
PDE6G	ENST00000574024.1 linkuse as main transcript	n.681T>G		non_coding_transcript_exon_variant	3/3	1

Frequencies

GnomAD3 genomes

AF:

0.0425

AC:

6461

AN:

152088

Hom.:

251

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0436

Gnomad AMI

AF:

0.115

Gnomad AMR

AF:

0.0372

Gnomad ASJ

AF:

0.0196

Gnomad EAS

AF:

0.211

Gnomad SAS

AF:

0.0643

Gnomad FIN

AF:

0.0118

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0340

Gnomad OTH

AF:

0.0311

GnomAD3 exomes

AF:

0.0492

AC:

6424

AN:

130468

Hom.:

353

AF XY:

0.0490

AC XY:

3491

AN XY:

71216

show subpopulations

Gnomad AFR exome

AF:

0.0434

Gnomad AMR exome

AF:

0.0237

Gnomad ASJ exome

AF:

0.0193

Gnomad EAS exome

AF:

0.211

Gnomad SAS exome

AF:

0.0566

Gnomad FIN exome

AF:

0.0132

Gnomad NFE exome

AF:

0.0350

Gnomad OTH exome

AF:

0.0380

GnomAD4 exome

AF:

0.0432

AC:

13060

AN:

302038

Hom.:

521

Cov.:

AF XY:

0.0446

AC XY:

7674

AN XY:

172148

show subpopulations

Gnomad4 AFR exome

AF:

0.0420

Gnomad4 AMR exome

AF:

0.0233

Gnomad4 ASJ exome

AF:

0.0184

Gnomad4 EAS exome

AF:

0.225

Gnomad4 SAS exome

AF:

0.0572

Gnomad4 FIN exome

AF:

0.0144

Gnomad4 NFE exome

AF:

0.0348

Gnomad4 OTH exome

AF:

0.0460

GnomAD4 genome

AF:

0.0425

AC:

6471

AN:

152206

Hom.:

252

Cov.:

AF XY:

0.0419

AC XY:

3118

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.0438

Gnomad4 AMR

AF:

0.0371

Gnomad4 ASJ

AF:

0.0196

Gnomad4 EAS

AF:

0.211

Gnomad4 SAS

AF:

0.0643

Gnomad4 FIN

AF:

0.0118

Gnomad4 NFE

AF:

0.0340

Gnomad4 OTH

AF:

0.0308

Alfa

AF:

0.0318

Hom.:

Bravo

AF:

0.0451

Asia WGS

AF:

0.131

AC:

456

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Retinitis pigmentosa

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.98

DANN

Benign

0.50

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