rs1866209

Positions:

• chr2-177742631-G-A
• chr2-177742631-G-C
• chr2-177742631-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016953.4(PDE11A):​c.1789-14459C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.716 in 151,994 control chromosomes in the GnomAD database, including 40,297 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 0.72 (40297 hom., cov: 31)
• Consequence: PDE11A NM_016953.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.116

Genes affected

PDE11A (HGNC:8773): (phosphodiesterase 11A) The 3',5'-cyclic nucleotides cAMP and cGMP function as second messengers in a wide variety of signal transduction pathways. 3',5'-cyclic nucleotide phosphodiesterases (PDEs) catalyze the hydrolysis of cAMP and cGMP to the corresponding 5'-monophosphates and provide a mechanism to downregulate cAMP and cGMP signaling. This gene encodes a member of the PDE protein superfamily. Mutations in this gene are a cause of Cushing disease and adrenocortical hyperplasia. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.837 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDE11A	NM_016953.4	c.1789-14459C>T		intron_variant		ENST00000286063.11	NP_058649.3
PDE11A	NM_001077196.2	c.457-14459C>T		intron_variant			NP_001070664.1
PDE11A	NM_001077197.2	c.1039-14459C>T		intron_variant			NP_001070665.1
PDE11A	NM_001077358.2	c.715-14459C>T		intron_variant			NP_001070826.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDE11A	ENST00000286063.11	c.1789-14459C>T		intron_variant		1	NM_016953.4	ENSP00000286063	P1

Frequencies

GnomAD3 genomes AF: 0.716 AC: 108742 AN: 151876 Hom.: 40272 Cov.: 31

Gnomad AFR AF: 0.510

Gnomad AMI AF: 0.779

Gnomad AMR AF: 0.780

Gnomad ASJ AF: 0.821

Gnomad EAS AF: 0.859

Gnomad SAS AF: 0.741

Gnomad FIN AF: 0.797

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.796

Gnomad OTH AF: 0.716

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

GnomAD4 genome AF: 0.716 AC: 108812 AN: 151994 Hom.: 40297 Cov.: 31 AF XY: 0.720 AC XY: 53479 AN XY: 74280

Gnomad4 AFR AF: 0.510

Gnomad4 AMR AF: 0.780

Gnomad4 ASJ AF: 0.821

Gnomad4 EAS AF: 0.858

Gnomad4 SAS AF: 0.739

Gnomad4 FIN AF: 0.797

Gnomad4 NFE AF: 0.796

Gnomad4 OTH AF: 0.718

Alfa AF: 0.772 Hom.: 43071

Bravo AF: 0.710

Asia WGS AF: 0.792 AC: 2751 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.6
DANN	Benign	0.60

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: rs1866209; hg19: chr2-178607359;