2-177663975-C-T

Variant names:

• chr2-177663975-C-T
• rs13025391
• NM_016953.4:c.2563-26G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_016953.4(PDE11A):​c.2563-26G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.859 in 1,477,516 control chromosomes in the GnomAD database, including 546,643 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.81 (51146 hom., cov: 32)
  • Exomes 𝑓: 0.86 (495497 hom.)
• Consequence: PDE11A NM_016953.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.271
• Publications: 15 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 2-177663975-C-T is Benign according to our data. Variant chr2-177663975-C-T is described in ClinVar as [Benign]. Clinvar id is 1326996.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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.2563-26G>A		intron_variant	Intron 18 of 19	ENST00000286063.11	NP_058649.3
PDE11A	NM_001077197.2	c.1813-26G>A		intron_variant	Intron 19 of 20		NP_001070665.1
PDE11A	NM_001077358.2	c.1489-26G>A		intron_variant	Intron 17 of 18		NP_001070826.1
PDE11A	NM_001077196.2	c.1231-26G>A		intron_variant	Intron 15 of 16		NP_001070664.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE11A	ENST00000286063.11	c.2563-26G>A		intron_variant	Intron 18 of 19	1	NM_016953.4	ENSP00000286063.5

Frequencies

GnomAD3 genomes AF: 0.814 AC: 123764 AN: 151980 Hom.: 51113 Cov.: 32

Gnomad AFR AF: 0.668

Gnomad AMI AF: 0.947

Gnomad AMR AF: 0.873

Gnomad ASJ AF: 0.806

Gnomad EAS AF: 0.977

Gnomad SAS AF: 0.896

Gnomad FIN AF: 0.887

Gnomad MID AF: 0.854

Gnomad NFE AF: 0.859

Gnomad OTH AF: 0.818

GnomAD2 exomes AF: 0.866 AC: 217005 AN: 250482 AF XY: 0.869

Gnomad AFR exome AF: 0.661

Gnomad AMR exome AF: 0.918

Gnomad ASJ exome AF: 0.810

Gnomad EAS exome AF: 0.982

Gnomad FIN exome AF: 0.889

Gnomad NFE exome AF: 0.855

Gnomad OTH exome AF: 0.857

GnomAD4 exome AF: 0.864 AC: 1145149 AN: 1325418 Hom.: 495497 Cov.: 20 AF XY: 0.865 AC XY: 576639 AN XY: 666818

African (AFR) AF: 0.663 AC: 20157 AN: 30380

American (AMR) AF: 0.913 AC: 40696 AN: 44552

Ashkenazi Jewish (ASJ) AF: 0.813 AC: 20505 AN: 25236

East Asian (EAS) AF: 0.987 AC: 38600 AN: 39090

South Asian (SAS) AF: 0.895 AC: 74536 AN: 83290

European-Finnish (FIN) AF: 0.887 AC: 47257 AN: 53302

Middle Eastern (MID) AF: 0.862 AC: 4742 AN: 5504

European-Non Finnish (NFE) AF: 0.861 AC: 850923 AN: 988258

Other (OTH) AF: 0.855 AC: 47733 AN: 55806

GnomAD4 genome AF: 0.814 AC: 123856 AN: 152098 Hom.: 51146 Cov.: 32 AF XY: 0.819 AC XY: 60917 AN XY: 74386

African (AFR) AF: 0.668 AC: 27673 AN: 41430

American (AMR) AF: 0.873 AC: 13346 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.806 AC: 2798 AN: 3472

East Asian (EAS) AF: 0.977 AC: 5062 AN: 5182

South Asian (SAS) AF: 0.897 AC: 4318 AN: 4816

European-Finnish (FIN) AF: 0.887 AC: 9400 AN: 10598

Middle Eastern (MID) AF: 0.854 AC: 251 AN: 294

European-Non Finnish (NFE) AF: 0.859 AC: 58414 AN: 67998

Other (OTH) AF: 0.820 AC: 1730 AN: 2110

Alfa AF: 0.844 Hom.: 207951

Bravo AF: 0.804

Asia WGS AF: 0.912 AC: 3168 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Pigmented nodular adrenocortical disease, primary, 2 Benign:1

Sep 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.88
DANN	Benign	0.59
PhyloP100		-0.27
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: rs13025391; hg19: chr2-178528703;