dbSNP rs2422324: PDE6C:c.2209-133G>C (chr10-93661926-G-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.27

Publications

3 publications found

Variant links:

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]

PDE6C Gene-Disease associations (from GenCC):

cone dystrophy 4
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
PDE6C-related retinopathy
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
cone dystrophy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
achromatopsia
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

PDE6C links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006204.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE6C	NM_006204.4	MANE Select	c.2209-133G>C		intron	N/A	NP_006195.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE6C	ENST00000371447.4	TSL:1 MANE Select	c.2209-133G>C		intron	N/A	ENSP00000360502.3	P51160
	PDE6C	ENST00000475427.2	TSL:2	n.-130G>C		upstream_gene	N/A

Frequencies

GnomAD3 genomes

AF:

0.279

AC:

42321

AN:

151874

Hom.:

6511

Cov.:

show subpopulations

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

show subpopulations

African (AFR)

AF:

0.419

AC:

6470

AN:

15442

American (AMR)

AF:

0.229

AC:

8230

AN:

35994

Ashkenazi Jewish (ASJ)

AF:

0.338

AC:

6666

AN:

19714

East Asian (EAS)

AF:

0.329

AC:

10545

AN:

32012

South Asian (SAS)

AF:

0.151

AC:

9674

AN:

63918

European-Finnish (FIN)

AF:

0.183

AC:

7706

AN:

42028

Middle Eastern (MID)

AF:

0.275

AC:

1099

AN:

3998

European-Non Finnish (NFE)

AF:

0.227

AC:

73299

AN:

322628

Other (OTH)

AF:

0.259

AC:

7905

AN:

30576

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

5129

10258

15387

20516

25645

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

554

1108

1662

2216

2770

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.279

AC:

42391

AN:

151994

Hom.:

6530

Cov.:

AF XY:

0.272

AC XY:

20168

AN XY:

74280

show subpopulations

African (AFR)

AF:

0.409

AC:

16928

AN:

41408

American (AMR)

AF:

0.241

AC:

3689

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.337

AC:

1171

AN:

3470

East Asian (EAS)

AF:

0.336

AC:

1735

AN:

5160

South Asian (SAS)

AF:

0.145

AC:

700

AN:

4820

European-Finnish (FIN)

AF:

0.180

AC:

1899

AN:

10568

Middle Eastern (MID)

AF:

0.353

AC:

103

AN:

292

European-Non Finnish (NFE)

AF:

0.226

AC:

15394

AN:

67984

Other (OTH)

AF:

0.283

AC:

597

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1489

2978

4467

5956

7445

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

424

848

1272

1696

2120

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.243

Hom.:

622

Bravo

AF:

0.296

Asia WGS

AF:

0.238

AC:

831

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

0.089

(source)

DANN

Benign

0.48

PhyloP100

-2.3

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over