Variant 17-81650504-A-G 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.*570T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.493 in 453,170 control chromosomes in the GnomAD database, including 60,926 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.50 ( 21091 hom., cov: 33)

Exomes 𝑓: 0.49 ( 39835 hom. )

Consequence

PDE6G
NM_002602.4 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.345

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.98).

BP6

Variant 17-81650504-A-G is Benign according to our data. Variant chr17-81650504-A-G is described in ClinVar as [Benign]. Clinvar id is 325850.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.971 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.*570T>C		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.*570T>C		3_prime_UTR_variant	4/4	1	NM_002602.4	ENSP00000328412.5		P18545
PDE6G	ENST00000574024.1 linkuse as main transcript	n.767T>C		non_coding_transcript_exon_variant	3/3	1

Frequencies

GnomAD3 genomes

AF:

0.501

AC:

76160

AN:

151954

Hom.:

21049

Cov.:

show subpopulations

Gnomad AFR

AF:

0.641

Gnomad AMI

AF:

0.484

Gnomad AMR

AF:

0.582

Gnomad ASJ

AF:

0.409

Gnomad EAS

AF:

0.994

Gnomad SAS

AF:

0.662

Gnomad FIN

AF:

0.338

Gnomad MID

AF:

0.411

Gnomad NFE

AF:

0.381

Gnomad OTH

AF:

0.470

GnomAD3 exomes

AF:

0.545

AC:

70825

AN:

130068

Hom.:

21898

AF XY:

0.538

AC XY:

38184

AN XY:

71002

show subpopulations

Gnomad AFR exome

AF:

0.657

Gnomad AMR exome

AF:

0.684

Gnomad ASJ exome

AF:

0.409

Gnomad EAS exome

AF:

0.998

Gnomad SAS exome

AF:

0.624

Gnomad FIN exome

AF:

0.340

Gnomad NFE exome

AF:

0.381

Gnomad OTH exome

AF:

0.462

GnomAD4 exome

AF:

0.488

AC:

146982

AN:

301098

Hom.:

39835

Cov.:

AF XY:

0.496

AC XY:

85074

AN XY:

171560

show subpopulations

Gnomad4 AFR exome

AF:

0.652

Gnomad4 AMR exome

AF:

0.685

Gnomad4 ASJ exome

AF:

0.407

Gnomad4 EAS exome

AF:

0.997

Gnomad4 SAS exome

AF:

0.619

Gnomad4 FIN exome

AF:

0.351

Gnomad4 NFE exome

AF:

0.385

Gnomad4 OTH exome

AF:

0.470

GnomAD4 genome

AF:

0.501

AC:

76262

AN:

152072

Hom.:

21091

Cov.:

AF XY:

0.505

AC XY:

37549

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.642

Gnomad4 AMR

AF:

0.583

Gnomad4 ASJ

AF:

0.409

Gnomad4 EAS

AF:

0.994

Gnomad4 SAS

AF:

0.662

Gnomad4 FIN

AF:

0.338

Gnomad4 NFE

AF:

0.381

Gnomad4 OTH

AF:

0.477

Alfa

AF:

0.390

Hom.:

14774

Bravo

AF:

0.528

Asia WGS

AF:

0.838

AC:

2913

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

-0.98

CADD

Benign

2.2

DANN

Benign

0.54

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