17-81650675-G-A

Position:

• chr17-81650675-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002602.4(PDE6G):​c.*399C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 457,192 control chromosomes in the GnomAD database, including 3,063 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (980 hom., cov: 32)
  • Exomes 𝑓: 0.11 (2083 hom.)
• Consequence: PDE6G NM_002602.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.162

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 17-81650675-G-A is Benign according to our data. Variant chr17-81650675-G-A is described in ClinVar as [Benign]. Clinvar id is 325854.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.136 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDE6G	NM_002602.4	c.*399C>T		3_prime_UTR_variant	4/4	ENST00000331056.10	NP_002593.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDE6G	ENST00000331056.10	c.*399C>T		3_prime_UTR_variant	4/4	1	NM_002602.4	ENSP00000328412.5
PDE6G	ENST00000574024.1	n.596C>T		non_coding_transcript_exon_variant	3/3	1

Frequencies

GnomAD3 genomes AF: 0.107 AC: 16212 AN: 152068 Hom.: 980 Cov.: 32

Gnomad AFR AF: 0.0664

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.0914

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0700

Gnomad FIN AF: 0.127

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.138

Gnomad OTH AF: 0.131

GnomAD3 exomes AF: 0.100 AC: 13022 AN: 129864 Hom.: 793 AF XY: 0.100 AC XY: 7099 AN XY: 70842

Gnomad AFR exome AF: 0.0603

Gnomad AMR exome AF: 0.0685

Gnomad ASJ exome AF: 0.148

Gnomad EAS exome AF: 0.000288

Gnomad SAS exome AF: 0.0767

Gnomad FIN exome AF: 0.143

Gnomad NFE exome AF: 0.139

Gnomad OTH exome AF: 0.123

GnomAD4 exome AF: 0.110 AC: 33422 AN: 305006 Hom.: 2083 Cov.: 0 AF XY: 0.106 AC XY: 18481 AN XY: 173544

Gnomad4 AFR exome AF: 0.0618

Gnomad4 AMR exome AF: 0.0686

Gnomad4 ASJ exome AF: 0.153

Gnomad4 EAS exome AF: 0.000313

Gnomad4 SAS exome AF: 0.0748

Gnomad4 FIN exome AF: 0.138

Gnomad4 NFE exome AF: 0.132

Gnomad4 OTH exome AF: 0.121

GnomAD4 genome AF: 0.107 AC: 16226 AN: 152186 Hom.: 980 Cov.: 32 AF XY: 0.104 AC XY: 7718 AN XY: 74394

Gnomad4 AFR AF: 0.0666

Gnomad4 AMR AF: 0.0912

Gnomad4 ASJ AF: 0.155

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.0705

Gnomad4 FIN AF: 0.127

Gnomad4 NFE AF: 0.138

Gnomad4 OTH AF: 0.130

Alfa AF: 0.122 Hom.: 215

Bravo AF: 0.104

Asia WGS AF: 0.0370 AC: 128 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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 13, 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	-0.90
CADD	Benign	1.5
DANN	Benign	0.76

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

Other links and lift over

dbSNP: rs13372; hg19: chr17-79617705;