PDE11A p.Met878Leu

Variant names:

• chr2-177663880-T-A
• NM_016953.4:c.2632A>T
• PDE11A p.Met878Leu

Your query was ambiguous. Multiple possible variants found:

• chr2-177663880-T-A
• chr2-177663880-T-G
• chr2-177663878-CAT-TAA
• chr2-177663878-CAT-AAG
• chr2-177663878-CAT-GAG
• chr2-177663878-CAT-TAG

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016953.4(PDE11A):​c.2632A>T​(p.Met878Leu) variant causes a missense 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. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M878V) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PDE11A NM_016953.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.45
• Publications: 0 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-AS1 (HGNC:40433): (PDE11A antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23976713).

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.2632A>T	p.Met878Leu	missense	Exon 19 of 20	NP_058649.3
	PDE11A	NM_001077197.2		c.1882A>T	p.Met628Leu	missense	Exon 20 of 21	NP_001070665.1	Q9HCR9-2
	PDE11A	NM_001077358.2		c.1558A>T	p.Met520Leu	missense	Exon 18 of 19	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.2632A>T	p.Met878Leu	missense	Exon 19 of 20	ENSP00000286063.5	Q9HCR9-1
	PDE11A	ENST00000358450.8	TSL:1	c.1882A>T	p.Met628Leu	missense	Exon 20 of 21	ENSP00000351232.4	Q9HCR9-2
	PDE11A	ENST00000409504.5	TSL:1	c.1558A>T	p.Met520Leu	missense	Exon 18 of 20	ENSP00000386539.1	Q9HCR9-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.031	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	15
DANN	Benign	0.68
DEOGEN2	Benign	0.090	T
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.38
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.64	T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-0.39	N
PhyloP100		1.4
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	0.23	N
REVEL	Uncertain	0.34
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Varity_R		0.084
gMVP		0.34
Mutation Taster		=87/13	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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.

Other links and lift over

hg19: chr2-178528608;