Variant chr2-177675565-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_016953.4(PDE11A):c.2424-47T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.807 in 1,452,882 control chromosomes in the GnomAD database, including 478,161 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.72 ( 42058 hom., cov: 31)

Exomes 𝑓: 0.82 ( 436103 hom. )

Consequence

PDE11A
NM_016953.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.37

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 -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.23).

BP6

Variant 2-177675565-A-G is Benign according to our data. Variant chr2-177675565-A-G is described in ClinVar as [Benign]. Clinvar id is 1326998.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.829 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDE11A	NM_016953.4 linkuse as main transcript	c.2424-47T>C		intron_variant		ENST00000286063.11	NP_058649.3
PDE11A-AS1	NR_136171.1 linkuse as main transcript	n.104+2140A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDE11A	ENST00000286063.11 linkuse as main transcript	c.2424-47T>C		intron_variant		1	NM_016953.4	ENSP00000286063	P1	Q9HCR9-1
PDE11A-AS1	ENST00000653062.1 linkuse as main transcript	n.365+21782A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.724

AC:

110035

AN:

151976

Hom.:

42051

Cov.:

show subpopulations

Gnomad AFR

AF:

0.450

Gnomad AMI

AF:

0.895

Gnomad AMR

AF:

0.816

Gnomad ASJ

AF:

0.834

Gnomad EAS

AF:

0.850

Gnomad SAS

AF:

0.820

Gnomad FIN

AF:

0.864

Gnomad MID

AF:

0.796

Gnomad NFE

AF:

0.823

Gnomad OTH

AF:

0.741

GnomAD3 exomes

AF:

0.813

AC:

196619

AN:

241954

Hom.:

81100

AF XY:

0.816

AC XY:

106573

AN XY:

130650

show subpopulations

Gnomad AFR exome

AF:

0.439

Gnomad AMR exome

AF:

0.893

Gnomad ASJ exome

AF:

0.829

Gnomad EAS exome

AF:

0.860

Gnomad SAS exome

AF:

0.809

Gnomad FIN exome

AF:

0.866

Gnomad NFE exome

AF:

0.822

Gnomad OTH exome

AF:

0.814

GnomAD4 exome

AF:

0.816

AC:

1061970

AN:

1300788

Hom.:

436103

Cov.:

AF XY:

0.817

AC XY:

535214

AN XY:

654984

show subpopulations

Gnomad4 AFR exome

AF:

0.441

Gnomad4 AMR exome

AF:

0.884

Gnomad4 ASJ exome

AF:

0.828

Gnomad4 EAS exome

AF:

0.868

Gnomad4 SAS exome

AF:

0.808

Gnomad4 FIN exome

AF:

0.867

Gnomad4 NFE exome

AF:

0.821

Gnomad4 OTH exome

AF:

0.803

GnomAD4 genome

AF:

0.724

AC:

110081

AN:

152094

Hom.:

42058

Cov.:

AF XY:

0.729

AC XY:

54225

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.450

Gnomad4 AMR

AF:

0.816

Gnomad4 ASJ

AF:

0.834

Gnomad4 EAS

AF:

0.850

Gnomad4 SAS

AF:

0.820

Gnomad4 FIN

AF:

0.864

Gnomad4 NFE

AF:

0.823

Gnomad4 OTH

AF:

0.741

Alfa

AF:

0.808

Hom.:

104577

Bravo

AF:

0.707

Asia WGS

AF:

0.798

AC:

2776

AN:

3478

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

-0.23

CADD

Benign

DANN

Benign

0.71

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