rs998059

Variant names:

• chr2-177747542-A-C
• rs998059
• NM_016953.4:c.1789-19370T>G

Your query was ambiguous. Multiple possible variants found:

• chr2-177747542-A-C
• chr2-177747542-A-T

Variant summary

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

The NM_016953.4(PDE11A):​c.1789-19370T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.715 in 152,134 control chromosomes in the GnomAD database, including 40,300 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 (40300 hom., cov: 32)
• Consequence: PDE11A NM_016953.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.983
• Publications: 8 publications found

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 Gene-Disease associations (from GenCC):

• pigmented nodular adrenocortical disease, primary, 2

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: Genomics England PanelApp, Laboratory for Molecular Medicine
• primary pigmented nodular adrenocortical disease

  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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.838 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016953.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE11A	NM_016953.4	MANE Select	c.1789-19370T>G		intron	N/A	NP_058649.3
	PDE11A	NM_001077197.2		c.1039-19370T>G		intron	N/A	NP_001070665.1	Q9HCR9-2
	PDE11A	NM_001077358.2		c.715-19370T>G		intron	N/A	NP_001070826.1	Q9HCR9-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE11A	ENST00000286063.11	TSL:1 MANE Select	c.1789-19370T>G		intron	N/A	ENSP00000286063.5	Q9HCR9-1
	PDE11A	ENST00000358450.8	TSL:1	c.1039-19370T>G		intron	N/A	ENSP00000351232.4	Q9HCR9-2
	PDE11A	ENST00000409504.5	TSL:1	c.715-19370T>G		intron	N/A	ENSP00000386539.1	Q9HCR9-3

Frequencies

GnomAD3 genomes AF: 0.715 AC: 108767 AN: 152016 Hom.: 40275 Cov.: 32

Gnomad AFR AF: 0.509

Gnomad AMI AF: 0.779

Gnomad AMR AF: 0.779

Gnomad ASJ AF: 0.821

Gnomad EAS AF: 0.859

Gnomad SAS AF: 0.741

Gnomad FIN AF: 0.797

Gnomad MID AF: 0.649

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: 0.715 AC: 108837 AN: 152134 Hom.: 40300 Cov.: 32 AF XY: 0.719 AC XY: 53499 AN XY: 74372

African (AFR) AF: 0.509 AC: 21108 AN: 41478

American (AMR) AF: 0.780 AC: 11930 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.821 AC: 2848 AN: 3470

East Asian (EAS) AF: 0.859 AC: 4443 AN: 5174

South Asian (SAS) AF: 0.740 AC: 3564 AN: 4818

European-Finnish (FIN) AF: 0.797 AC: 8439 AN: 10590

Middle Eastern (MID) AF: 0.643 AC: 189 AN: 294

European-Non Finnish (NFE) AF: 0.796 AC: 54089 AN: 67992

Other (OTH) AF: 0.718 AC: 1517 AN: 2112

Alfa AF: 0.764 Hom.: 22004

Bravo AF: 0.710

Asia WGS AF: 0.792 AC: 2751 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.5
DANN	Benign	0.35
PhyloP100		0.98
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: rs998059; hg19: chr2-178612270;