17-81652196-C-T

Variant names:

• chr17-81652196-C-T
• rs7406828
• NM_002602.4:c.147-511G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002602.4(PDE6G):​c.147-511G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.438 in 150,982 control chromosomes in the GnomAD database, including 15,533 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.44 (15533 hom., cov: 32)
• Consequence: PDE6G NM_002602.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.419
• Publications: 12 publications found

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 Gene-Disease associations (from GenCC):

• retinitis pigmentosa 57

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• retinitis pigmentosa

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.761 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE6G	NM_002602.4	c.147-511G>A		intron_variant	Intron 2 of 3	ENST00000331056.10	NP_002593.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE6G	ENST00000331056.10	c.147-511G>A		intron_variant	Intron 2 of 3	1	NM_002602.4	ENSP00000328412.5

Frequencies

GnomAD3 genomes AF: 0.438 AC: 66074 AN: 150858 Hom.: 15498 Cov.: 32

Gnomad AFR AF: 0.527

Gnomad AMI AF: 0.365

Gnomad AMR AF: 0.537

Gnomad ASJ AF: 0.387

Gnomad EAS AF: 0.782

Gnomad SAS AF: 0.594

Gnomad FIN AF: 0.328

Gnomad MID AF: 0.385

Gnomad NFE AF: 0.346

Gnomad OTH AF: 0.419

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.438 AC: 66151 AN: 150982 Hom.: 15533 Cov.: 32 AF XY: 0.443 AC XY: 32652 AN XY: 73726

African (AFR) AF: 0.527 AC: 21650 AN: 41116

American (AMR) AF: 0.538 AC: 8175 AN: 15204

Ashkenazi Jewish (ASJ) AF: 0.387 AC: 1330 AN: 3438

East Asian (EAS) AF: 0.782 AC: 4002 AN: 5120

South Asian (SAS) AF: 0.593 AC: 2836 AN: 4782

European-Finnish (FIN) AF: 0.328 AC: 3418 AN: 10422

Middle Eastern (MID) AF: 0.377 AC: 110 AN: 292

European-Non Finnish (NFE) AF: 0.346 AC: 23408 AN: 67612

Other (OTH) AF: 0.426 AC: 894 AN: 2098

Alfa AF: 0.396 Hom.: 3095

Bravo AF: 0.460

Asia WGS AF: 0.699 AC: 2433 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.7
DANN	Benign	0.64
PhyloP100		-0.42
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7406828; hg19: chr17-79619226;