2-177641710-C-G

Variant names:

• chr2-177641710-C-G
• rs1997207
• NM_016953.4:c.2647-12148G>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.2647-12148G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.87 in 152,274 control chromosomes in the GnomAD database, including 57,791 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 0.87 (57791 hom., cov: 33)
• Consequence: PDE11A NM_016953.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.134
• 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.954 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE11A	NM_016953.4	c.2647-12148G>C		intron_variant	Intron 19 of 19	ENST00000286063.11	NP_058649.3
PDE11A	NM_001077197.2	c.1897-12148G>C		intron_variant	Intron 20 of 20		NP_001070665.1
PDE11A	NM_001077358.2	c.1573-12148G>C		intron_variant	Intron 18 of 18		NP_001070826.1
PDE11A	NM_001077196.2	c.1315-12148G>C		intron_variant	Intron 16 of 16		NP_001070664.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE11A	ENST00000286063.11	c.2647-12148G>C		intron_variant	Intron 19 of 19	1	NM_016953.4	ENSP00000286063.5

Frequencies

GnomAD3 genomes AF: 0.870 AC: 132441 AN: 152156 Hom.: 57748 Cov.: 33

Gnomad AFR AF: 0.838

Gnomad AMI AF: 0.947

Gnomad AMR AF: 0.894

Gnomad ASJ AF: 0.821

Gnomad EAS AF: 0.977

Gnomad SAS AF: 0.905

Gnomad FIN AF: 0.892

Gnomad MID AF: 0.877

Gnomad NFE AF: 0.873

Gnomad OTH AF: 0.865

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

GnomAD4 genome AF: 0.870 AC: 132544 AN: 152274 Hom.: 57791 Cov.: 33 AF XY: 0.873 AC XY: 65020 AN XY: 74450

African (AFR) AF: 0.838 AC: 34812 AN: 41542

American (AMR) AF: 0.894 AC: 13684 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.821 AC: 2850 AN: 3472

East Asian (EAS) AF: 0.977 AC: 5066 AN: 5186

South Asian (SAS) AF: 0.905 AC: 4368 AN: 4824

European-Finnish (FIN) AF: 0.892 AC: 9462 AN: 10606

Middle Eastern (MID) AF: 0.878 AC: 258 AN: 294

European-Non Finnish (NFE) AF: 0.873 AC: 59351 AN: 68022

Other (OTH) AF: 0.866 AC: 1829 AN: 2112

Alfa AF: 0.868 Hom.: 6713

Bravo AF: 0.867

Asia WGS AF: 0.931 AC: 3234 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.7
DANN	Benign	0.58
PhyloP100		0.13
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: rs1997207; hg19: chr2-178506438;