2-177675565-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The NM_016953.4(PDE11A):c.2424-47T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.807 in 1,452,882 control chromosomes in the GnomAD database, including 478,161 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.72 (42058 hom., cov: 31)
  • Exomes 𝑓: 0.82 (436103 hom.)
• Consequence: PDE11A NM_016953.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.37

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]

PDE11A-AS1 (HGNC:40433): (PDE11A antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.23).
• BP6: Variant 2-177675565-A-G is Benign according to our data. Variant chr2-177675565-A-G is described in ClinVar as [Benign]. Clinvar id is 1326998.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.829 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDE11A	NM_016953.4	c.2424-47T>C		intron_variant		ENST00000286063.11
PDE11A-AS1	NR_136171.1	n.104+2140A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDE11A	ENST00000286063.11	c.2424-47T>C		intron_variant		1	NM_016953.4	P1
PDE11A-AS1	ENST00000653062.1	n.365+21782A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.724 AC: 110035 AN: 151976 Hom.: 42051 Cov.: 31

Gnomad AFR AF: 0.450

Gnomad AMI AF: 0.895

Gnomad AMR AF: 0.816

Gnomad ASJ AF: 0.834

Gnomad EAS AF: 0.850

Gnomad SAS AF: 0.820

Gnomad FIN AF: 0.864

Gnomad MID AF: 0.796

Gnomad NFE AF: 0.823

Gnomad OTH AF: 0.741

GnomAD3 exomes AF: 0.813 AC: 196619 AN: 241954 Hom.: 81100 AF XY: 0.816 AC XY: 106573 AN XY: 130650

Gnomad AFR exome AF: 0.439

Gnomad AMR exome AF: 0.893

Gnomad ASJ exome AF: 0.829

Gnomad EAS exome AF: 0.860

Gnomad SAS exome AF: 0.809

Gnomad FIN exome AF: 0.866

Gnomad NFE exome AF: 0.822

Gnomad OTH exome AF: 0.814

GnomAD4 exome AF: 0.816 AC: 1061970 AN: 1300788 Hom.: 436103 Cov.: 18 AF XY: 0.817 AC XY: 535214 AN XY: 654984

Gnomad4 AFR exome AF: 0.441

Gnomad4 AMR exome AF: 0.884

Gnomad4 ASJ exome AF: 0.828

Gnomad4 EAS exome AF: 0.868

Gnomad4 SAS exome AF: 0.808

Gnomad4 FIN exome AF: 0.867

Gnomad4 NFE exome AF: 0.821

Gnomad4 OTH exome AF: 0.803

GnomAD4 genome AF: 0.724 AC: 110081 AN: 152094 Hom.: 42058 Cov.: 31 AF XY: 0.729 AC XY: 54225 AN XY: 74342

Gnomad4 AFR AF: 0.450

Gnomad4 AMR AF: 0.816

Gnomad4 ASJ AF: 0.834

Gnomad4 EAS AF: 0.850

Gnomad4 SAS AF: 0.820

Gnomad4 FIN AF: 0.864

Gnomad4 NFE AF: 0.823

Gnomad4 OTH AF: 0.741

Alfa AF: 0.808 Hom.: 104577

Bravo AF: 0.707

Asia WGS AF: 0.798 AC: 2776 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Pigmented nodular adrenocortical disease, primary, 2 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.23
Cadd	Benign	14
Dann	Benign	0.71

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: rs3770016; hg19: chr2-178540293;