rs2422324

Positions:

• chr10-93661926-G-C

Variant summary

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

The NM_006204.4(PDE6C):​c.2209-133G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.242 in 718,304 control chromosomes in the GnomAD database, including 22,974 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.28 (6530 hom., cov: 32)
  • Exomes 𝑓: 0.23 (16444 hom.)
• Consequence: PDE6C NM_006204.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.27

Genes affected

PDE6C (HGNC:8787): (phosphodiesterase 6C) This gene encodes the alpha-prime subunit of cone phosphodiesterase, which is composed of a homodimer of two alpha-prime subunits and 3 smaller proteins of 11, 13, and 15 kDa. Mutations in this gene are associated with cone dystrophy type 4 (COD4). [provided by RefSeq, Mar 2010]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant 10-93661926-G-C is Benign according to our data. Variant chr10-93661926-G-C is described in ClinVar as [Benign]. Clinvar id is 1292951.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.404 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDE6C	NM_006204.4	c.2209-133G>C		intron_variant		ENST00000371447.4	NP_006195.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDE6C	ENST00000371447.4	c.2209-133G>C		intron_variant		1	NM_006204.4	ENSP00000360502	P1

Frequencies

GnomAD3 genomes AF: 0.279 AC: 42321 AN: 151874 Hom.: 6511 Cov.: 32

Gnomad AFR AF: 0.408

Gnomad AMI AF: 0.193

Gnomad AMR AF: 0.242

Gnomad ASJ AF: 0.337

Gnomad EAS AF: 0.335

Gnomad SAS AF: 0.146

Gnomad FIN AF: 0.180

Gnomad MID AF: 0.347

Gnomad NFE AF: 0.226

Gnomad OTH AF: 0.283

GnomAD4 exome AF: 0.232 AC: 131594 AN: 566310 Hom.: 16444 AF XY: 0.227 AC XY: 69713 AN XY: 307696

Gnomad4 AFR exome AF: 0.419

Gnomad4 AMR exome AF: 0.229

Gnomad4 ASJ exome AF: 0.338

Gnomad4 EAS exome AF: 0.329

Gnomad4 SAS exome AF: 0.151

Gnomad4 FIN exome AF: 0.183

Gnomad4 NFE exome AF: 0.227

Gnomad4 OTH exome AF: 0.259

GnomAD4 genome AF: 0.279 AC: 42391 AN: 151994 Hom.: 6530 Cov.: 32 AF XY: 0.272 AC XY: 20168 AN XY: 74280

Gnomad4 AFR AF: 0.409

Gnomad4 AMR AF: 0.241

Gnomad4 ASJ AF: 0.337

Gnomad4 EAS AF: 0.336

Gnomad4 SAS AF: 0.145

Gnomad4 FIN AF: 0.180

Gnomad4 NFE AF: 0.226

Gnomad4 OTH AF: 0.283

Alfa AF: 0.243 Hom.: 622

Bravo AF: 0.296

Asia WGS AF: 0.238 AC: 831 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.089
DANN	Benign	0.48

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: rs2422324; hg19: chr10-95421683; COSMIC: COSV65117327; COSMIC: COSV65117327;