Genetic Variant PDE11A:c.1071+45915C>T (chr2-177968387-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is . The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_016953.4(PDE11A):c.1071+45915C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 152,148 control chromosomes in the GnomAD database, including 1,974 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 0.16 ( 1974 hom., cov: 32)

Consequence

PDE11A
NM_016953.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.202

Publications

4 publications found

Variant links:

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: PanelApp Australia, Genomics England PanelApp, Laboratory for Molecular Medicine
primary pigmented nodular adrenocortical disease
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

PDE11A links:

ENSG00000236664 (HGNC:):

ENSG00000236664 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_016953.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.228 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.1071+45915C>T		intron	N/A	NP_058649.3
	PDE11A	NM_001077197.2		c.321+45915C>T		intron	N/A	NP_001070665.1	Q9HCR9-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PDE11A	ENST00000286063.11	TSL:1 MANE Select	c.1071+45915C>T	intron	N/A	ENSP00000286063.5	Q9HCR9-1
PDE11A	ENST00000358450.8	TSL:1	c.321+45915C>T	intron	N/A	ENSP00000351232.4	Q9HCR9-2
ENSG00000236664	ENST00000457053.1	TSL:3	n.84-15106C>T	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.158

AC:

24059

AN:

152030

Hom.:

1970

Cov.:

show subpopulations

Gnomad AFR

AF:

0.203

Gnomad AMI

AF:

0.155

Gnomad AMR

AF:

0.138

Gnomad ASJ

AF:

0.196

Gnomad EAS

AF:

0.162

Gnomad SAS

AF:

0.240

Gnomad FIN

AF:

0.0791

Gnomad MID

AF:

0.258

Gnomad NFE

AF:

0.139

Gnomad OTH

AF:

0.180

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

GnomAD4 genome

AF:

0.158

AC:

24086

AN:

152148

Hom.:

1974

Cov.:

AF XY:

0.156

AC XY:

11638

AN XY:

74382

show subpopulations

African (AFR)

AF:

0.203

AC:

8429

AN:

41484

American (AMR)

AF:

0.138

AC:

2111

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.196

AC:

680

AN:

3462

East Asian (EAS)

AF:

0.163

AC:

843

AN:

5186

South Asian (SAS)

AF:

0.240

AC:

1157

AN:

4824

European-Finnish (FIN)

AF:

0.0791

AC:

839

AN:

10604

Middle Eastern (MID)

AF:

0.260

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.139

AC:

9432

AN:

67996

Other (OTH)

AF:

0.179

AC:

378

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1041

2082

3123

4164

5205

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

272

544

816

1088

1360

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.150

Hom.:

945

Bravo

AF:

0.162

Asia WGS

AF:

0.189

AC:

656

AN:

3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

2.3

(source)

DANN

Benign

0.21

PhyloP100

-0.20

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over