rs2785137

Variant names:

• chr10-93626450-G-A
• rs2785137
• NM_006204.4:c.940-190G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-93626450-G-A
• chr10-93626450-G-C

Variant summary

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

The NM_006204.4(PDE6C):​c.940-190G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.367 in 152,024 control chromosomes in the GnomAD database, including 10,468 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 0.37 (10468 hom., cov: 32)
• Consequence: PDE6C NM_006204.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.179
• Publications: 7 publications found

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
• inherited retinal dystrophy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• cone dystrophy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• achromatopsia

  Inheritance: AR 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.449 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE6C	NM_006204.4	c.940-190G>A		intron_variant	Intron 5 of 21	ENST00000371447.4	NP_006195.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE6C	ENST00000371447.4	c.940-190G>A		intron_variant	Intron 5 of 21	1	NM_006204.4	ENSP00000360502.3

Frequencies

GnomAD3 genomes AF: 0.367 AC: 55751 AN: 151906 Hom.: 10447 Cov.: 32

Gnomad AFR AF: 0.428

Gnomad AMI AF: 0.429

Gnomad AMR AF: 0.386

Gnomad ASJ AF: 0.302

Gnomad EAS AF: 0.465

Gnomad SAS AF: 0.304

Gnomad FIN AF: 0.327

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.332

Gnomad OTH AF: 0.348

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

GnomAD4 genome AF: 0.367 AC: 55821 AN: 152024 Hom.: 10468 Cov.: 32 AF XY: 0.366 AC XY: 27209 AN XY: 74318

African (AFR) AF: 0.429 AC: 17768 AN: 41460

American (AMR) AF: 0.386 AC: 5895 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.302 AC: 1047 AN: 3466

East Asian (EAS) AF: 0.465 AC: 2403 AN: 5168

South Asian (SAS) AF: 0.302 AC: 1452 AN: 4810

European-Finnish (FIN) AF: 0.327 AC: 3456 AN: 10568

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.332 AC: 22579 AN: 67952

Other (OTH) AF: 0.351 AC: 740 AN: 2110

Alfa AF: 0.346 Hom.: 21901

Bravo AF: 0.377

Asia WGS AF: 0.407 AC: 1414 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.0
DANN	Benign	0.53
PhyloP100		0.18
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: rs2785137; hg19: chr10-95386207;