rs1405645

Positions:

• chr2-177988651-G-A
• chr2-177988651-G-C

Variant summary

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

The NM_016953.4(PDE11A):​c.1071+25651C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.425 in 152,016 control chromosomes in the GnomAD database, including 16,903 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 0.42 (16903 hom., cov: 32)
• Consequence: PDE11A NM_016953.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.399

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.552 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDE11A	NM_016953.4	c.1071+25651C>T		intron_variant		ENST00000286063.11
PDE11A	NM_001077197.2	c.321+25651C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDE11A	ENST00000286063.11	c.1071+25651C>T		intron_variant		1	NM_016953.4	P1
PDE11A	ENST00000358450.8	c.321+25651C>T		intron_variant		1
	ENST00000457053.1	n.83+23256C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.425 AC: 64577 AN: 151898 Hom.: 16894 Cov.: 32

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.318

Gnomad AMR AF: 0.561

Gnomad ASJ AF: 0.471

Gnomad EAS AF: 0.546

Gnomad SAS AF: 0.439

Gnomad FIN AF: 0.676

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.535

Gnomad OTH AF: 0.410

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

GnomAD4 genome AF: 0.425 AC: 64590 AN: 152016 Hom.: 16903 Cov.: 32 AF XY: 0.432 AC XY: 32106 AN XY: 74276

Gnomad4 AFR AF: 0.112

Gnomad4 AMR AF: 0.562

Gnomad4 ASJ AF: 0.471

Gnomad4 EAS AF: 0.545

Gnomad4 SAS AF: 0.438

Gnomad4 FIN AF: 0.676

Gnomad4 NFE AF: 0.535

Gnomad4 OTH AF: 0.413

Alfa AF: 0.488 Hom.: 6435

Bravo AF: 0.406

Asia WGS AF: 0.514 AC: 1785 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.3
DANN	Benign	0.50

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: rs1405645; hg19: chr2-178853378;