rs2983517

Variant names:

• chr6-165638243-T-C
• rs2983517
• NM_001385079.1:c.865+23704A>G

Variant summary

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

The NM_001385079.1(PDE10A):​c.865+23704A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.24 in 151,982 control chromosomes in the GnomAD database, including 4,582 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 0.24 (4582 hom., cov: 32)
• Consequence: PDE10A NM_001385079.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.913
• Publications: 2 publications found

Genes affected

PDE10A (HGNC:8772): (phosphodiesterase 10A) The protein encoded by this gene belongs to the cyclic nucleotide phosphodiesterase family. It plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides. This protein can hydrolyze both cAMP and cGMP to the corresponding nucleoside 5' monophosphate, but has higher affinity for cAMP, and is more efficient with cAMP as substrate. Alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, Dec 2011]

PDE10A Gene-Disease associations (from GenCC):

• striatal degeneration, autosomal dominant 2

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Genomics England PanelApp, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• dyskinesia, limb and orofacial, infantile-onset

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Genomics England PanelApp, Ambry Genetics
• infantile-onset generalized dyskinesia with orofacial involvement

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• childhood-onset benign chorea with striatal involvement

  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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.264 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE10A	NM_001385079.1	c.865+23704A>G		intron_variant	Intron 1 of 21	ENST00000539869.4	NP_001372008.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE10A	ENST00000539869.4	c.865+23704A>G		intron_variant	Intron 1 of 21	1	NM_001385079.1	ENSP00000438284.3

Frequencies

GnomAD3 genomes AF: 0.240 AC: 36419 AN: 151864 Hom.: 4582 Cov.: 32

Gnomad AFR AF: 0.227

Gnomad AMI AF: 0.357

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.308

Gnomad EAS AF: 0.00657

Gnomad SAS AF: 0.238

Gnomad FIN AF: 0.235

Gnomad MID AF: 0.420

Gnomad NFE AF: 0.267

Gnomad OTH AF: 0.263

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

GnomAD4 genome AF: 0.240 AC: 36430 AN: 151982 Hom.: 4582 Cov.: 32 AF XY: 0.238 AC XY: 17683 AN XY: 74302

African (AFR) AF: 0.227 AC: 9405 AN: 41456

American (AMR) AF: 0.205 AC: 3140 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.308 AC: 1068 AN: 3472

East Asian (EAS) AF: 0.00659 AC: 34 AN: 5160

South Asian (SAS) AF: 0.238 AC: 1148 AN: 4818

European-Finnish (FIN) AF: 0.235 AC: 2474 AN: 10540

Middle Eastern (MID) AF: 0.397 AC: 115 AN: 290

European-Non Finnish (NFE) AF: 0.267 AC: 18162 AN: 67940

Other (OTH) AF: 0.264 AC: 558 AN: 2114

Alfa AF: 0.240 Hom.: 833

Bravo AF: 0.238

Asia WGS AF: 0.136 AC: 471 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.56
DANN	Benign	0.56
PhyloP100		-0.91

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: rs2983517; hg19: chr6-166051731; COSMIC: COSV64840530;