Variant chr2-177663975-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.271

Variant links:

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 links:

PDE11A-AS1 (HGNC:40433): (PDE11A antisense RNA 1)

PDE11A-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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	Effect	MANE	Protein
PDE11A	NM_016953.4 linkuse as main transcript	c.2563-26G>A	intron_variant	ENST00000286063.11	NP_058649.3
PDE11A	NM_001077196.2 linkuse as main transcript	c.1231-26G>A	intron_variant		NP_001070664.1
PDE11A	NM_001077197.2 linkuse as main transcript	c.1813-26G>A	intron_variant		NP_001070665.1
PDE11A	NM_001077358.2 linkuse as main transcript	c.1489-26G>A	intron_variant		NP_001070826.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDE11A	ENST00000286063.11 linkuse as main transcript	c.2563-26G>A		intron_variant		1	NM_016953.4	ENSP00000286063	P1	Q9HCR9-1
PDE11A-AS1	ENST00000653062.1 linkuse as main transcript	n.365+10192C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.814

AC:

123764

AN:

151980

Hom.:

51113

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.866

AC:

217005

AN:

250482

Hom.:

94578

AF XY:

0.869

AC XY:

117560

AN XY:

135348

show subpopulations

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 SAS exome

AF:

0.895

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.:

AF XY:

0.865

AC XY:

576639

AN XY:

666818

show subpopulations

Gnomad4 AFR exome

AF:

0.663

Gnomad4 AMR exome

AF:

0.913

Gnomad4 ASJ exome

AF:

0.813

Gnomad4 EAS exome

AF:

0.987

Gnomad4 SAS exome

AF:

0.895

Gnomad4 FIN exome

AF:

0.887

Gnomad4 NFE exome

AF:

0.861

Gnomad4 OTH exome

AF:

0.855

GnomAD4 genome

AF:

0.814

AC:

123856

AN:

152098

Hom.:

51146

Cov.:

AF XY:

0.819

AC XY:

60917

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.668

Gnomad4 AMR

AF:

0.873

Gnomad4 ASJ

AF:

0.806

Gnomad4 EAS

AF:

0.977

Gnomad4 SAS

AF:

0.897

Gnomad4 FIN

AF:

0.887

Gnomad4 NFE

AF:

0.859

Gnomad4 OTH

AF:

0.820

Alfa

AF:

0.851

Hom.:

95480

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

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Pigmented nodular adrenocortical disease, primary, 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.88

DANN

Benign

0.59

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over