Variant chr2-177680861-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_016953.4(PDE11A):c.2388C>T(p.Tyr796=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00413 in 1,592,232 control chromosomes in the GnomAD database, including 224 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.022 ( 106 hom., cov: 33)

Exomes 𝑓: 0.0023 ( 118 hom. )

Consequence

PDE11A
NM_016953.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.749

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant 2-177680861-G-A is Benign according to our data. Variant chr2-177680861-G-A is described in ClinVar as [Benign]. Clinvar id is 787776.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.749 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0738 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.2388C>T	p.Tyr796=	synonymous_variant	16/20	ENST00000286063.11	NP_058649.3
PDE11A-AS1	NR_136171.1 linkuse as main transcript	n.104+7436G>A		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.2388C>T	p.Tyr796=	synonymous_variant	16/20	1	NM_016953.4	ENSP00000286063	P1	Q9HCR9-1
PDE11A-AS1	ENST00000653062.1 linkuse as main transcript	n.366-17568G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.0219

AC:

3319

AN:

151798

Hom.:

106

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0759

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00728

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.000500

Gnomad OTH

AF:

0.0158

GnomAD3 exomes

AF:

0.00568

AC:

1419

AN:

250010

Hom.:

AF XY:

0.00429

AC XY:

579

AN XY:

135106

show subpopulations

Gnomad AFR exome

AF:

0.0774

Gnomad AMR exome

AF:

0.00337

Gnomad ASJ exome

AF:

0.000298

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000296

Gnomad FIN exome

AF:

0.0000467

Gnomad NFE exome

AF:

0.000168

Gnomad OTH exome

AF:

0.00279

GnomAD4 exome

AF:

0.00226

AC:

3250

AN:

1440318

Hom.:

118

Cov.:

AF XY:

0.00199

AC XY:

1430

AN XY:

717950

show subpopulations

Gnomad4 AFR exome

AF:

0.0785

Gnomad4 AMR exome

AF:

0.00410

Gnomad4 ASJ exome

AF:

0.000154

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.000210

Gnomad4 FIN exome

AF:

0.0000565

Gnomad4 NFE exome

AF:

0.000130

Gnomad4 OTH exome

AF:

0.00499

GnomAD4 genome

AF:

0.0219

AC:

3331

AN:

151914

Hom.:

106

Cov.:

AF XY:

0.0214

AC XY:

1591

AN XY:

74236

show subpopulations

Gnomad4 AFR

AF:

0.0760

Gnomad4 AMR

AF:

0.00721

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000500

Gnomad4 OTH

AF:

0.0157

Alfa

AF:

0.0125

Hom.:

Bravo

AF:

0.0245

Asia WGS

AF:

0.00520

AC:

AN:

3474

EpiCase

AF:

0.000327

EpiControl

AF:

0.000415

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

PDE11A-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 25, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

7.4

DANN

Benign

0.41

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