rs13413635

Variant names:

• chr2-177815704-A-G
• rs13413635
• NM_016953.4:c.1737+1125T>C

Variant summary

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

The NM_016953.4(PDE11A):​c.1737+1125T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.292 in 152,002 control chromosomes in the GnomAD database, including 7,290 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 0.29 (7290 hom., cov: 32)
• Consequence: PDE11A NM_016953.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.116
• Publications: 7 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.445 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.1737+1125T>C		intron	N/A	NP_058649.3
	PDE11A	NM_001077197.2		c.987+1125T>C		intron	N/A	NP_001070665.1	Q9HCR9-2
	PDE11A	NM_001077358.2		c.663+1125T>C		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.1737+1125T>C		intron	N/A	ENSP00000286063.5	Q9HCR9-1
	PDE11A	ENST00000358450.8	TSL:1	c.987+1125T>C		intron	N/A	ENSP00000351232.4	Q9HCR9-2
	PDE11A	ENST00000409504.5	TSL:1	c.663+1125T>C		intron	N/A	ENSP00000386539.1	Q9HCR9-3

Frequencies

GnomAD3 genomes AF: 0.292 AC: 44381 AN: 151882 Hom.: 7279 Cov.: 32

Gnomad AFR AF: 0.450

Gnomad AMI AF: 0.442

Gnomad AMR AF: 0.222

Gnomad ASJ AF: 0.310

Gnomad EAS AF: 0.207

Gnomad SAS AF: 0.239

Gnomad FIN AF: 0.171

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.238

Gnomad OTH AF: 0.302

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

GnomAD4 genome AF: 0.292 AC: 44423 AN: 152002 Hom.: 7290 Cov.: 32 AF XY: 0.289 AC XY: 21484 AN XY: 74328

African (AFR) AF: 0.450 AC: 18641 AN: 41406

American (AMR) AF: 0.222 AC: 3388 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.310 AC: 1073 AN: 3462

East Asian (EAS) AF: 0.207 AC: 1073 AN: 5178

South Asian (SAS) AF: 0.239 AC: 1153 AN: 4828

European-Finnish (FIN) AF: 0.171 AC: 1812 AN: 10598

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.238 AC: 16165 AN: 67956

Other (OTH) AF: 0.300 AC: 632 AN: 2108

Alfa AF: 0.294 Hom.: 4255

Bravo AF: 0.305

Asia WGS AF: 0.205 AC: 711 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.0
DANN	Benign	0.81
PhyloP100		-0.12
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: rs13413635; hg19: chr2-178680431;