NM_016953.4:c.1789-15098A>T

Variant names:

• chr2-177743270-T-A
• rs1370656
• NM_016953.4:c.1789-15098A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_016953.4(PDE11A):​c.1789-15098A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
• Consequence: PDE11A NM_016953.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.685
• Publications: 5 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE11A	NM_016953.4	MANE Select	c.1789-15098A>T		intron	N/A	NP_058649.3
	PDE11A	NM_001077197.2		c.1039-15098A>T		intron	N/A	NP_001070665.1
	PDE11A	NM_001077358.2		c.715-15098A>T		intron	N/A	NP_001070826.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE11A	ENST00000286063.11	TSL:1 MANE Select	c.1789-15098A>T		intron	N/A	ENSP00000286063.5
	PDE11A	ENST00000358450.8	TSL:1	c.1039-15098A>T		intron	N/A	ENSP00000351232.4
	PDE11A	ENST00000409504.5	TSL:1	c.715-15098A>T		intron	N/A	ENSP00000386539.1

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.67
DANN	Benign	0.098
PhyloP100		-0.69

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: rs1370656; hg19: chr2-178607998;