Variant 2-177629445-G-GGGA details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 1P and 16B. PM4_SupportingBP6_Very_StrongBA1

The NM_016953.4(PDE11A):c.2761_2763dupTCC(p.Ser921dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.718 in 1,612,458 control chromosomes in the GnomAD database, including 425,175 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.62 ( 32198 hom., cov: 0)

Exomes 𝑓: 0.73 ( 392977 hom. )

Consequence

PDE11A
NM_016953.4 conservative_inframe_insertion

Scores

Not classified

Clinical Significance

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

Conservation

PhyloP100: 0.967

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 (HGNC:):

PDE11A links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_016953.4. Strenght limited to Supporting due to length of the change: 1aa.

BP6

Variant 2-177629445-G-GGGA is Benign according to our data. Variant chr2-177629445-G-GGGA is described in ClinVar as [Benign]. Clinvar id is 1230360.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.736 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.2761_2763dupTCC	p.Ser921dup	conservative_inframe_insertion	20/20	ENST00000286063.11	NP_058649.3	Q9HCR9-1
PDE11A	NM_001077197.2 linkuse as main transcript	c.2011_2013dupTCC	p.Ser671dup	conservative_inframe_insertion	21/21		NP_001070665.1	Q9HCR9-2
PDE11A	NM_001077358.2 linkuse as main transcript	c.1687_1689dupTCC	p.Ser563dup	conservative_inframe_insertion	19/19		NP_001070826.1	Q9HCR9-3
PDE11A	NM_001077196.2 linkuse as main transcript	c.1429_1431dupTCC	p.Ser477dup	conservative_inframe_insertion	17/17		NP_001070664.1	Q9HCR9-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDE11A	ENST00000286063.11 linkuse as main transcript	c.2761_2763dupTCC	p.Ser921dup	conservative_inframe_insertion	20/20	1	NM_016953.4	ENSP00000286063.5		Q9HCR9-1

Frequencies

GnomAD3 genomes

AF:

0.619

AC:

93967

AN:

151790

Hom.:

32188

Cov.:

show subpopulations

Gnomad AFR

AF:

0.302

Gnomad AMI

AF:

0.641

Gnomad AMR

AF:

0.742

Gnomad ASJ

AF:

0.677

Gnomad EAS

AF:

0.673

Gnomad SAS

AF:

0.662

Gnomad FIN

AF:

0.826

Gnomad MID

AF:

0.589

Gnomad NFE

AF:

0.742

Gnomad OTH

AF:

0.635

GnomAD3 exomes

AF:

0.709

AC:

178403

AN:

251470

Hom.:

65416

AF XY:

0.708

AC XY:

96230

AN XY:

135902

show subpopulations

Gnomad AFR exome

AF:

0.289

Gnomad AMR exome

AF:

0.829

Gnomad ASJ exome

AF:

0.664

Gnomad EAS exome

AF:

0.689

Gnomad SAS exome

AF:

0.649

Gnomad FIN exome

AF:

0.821

Gnomad NFE exome

AF:

0.735

Gnomad OTH exome

AF:

0.712

GnomAD4 exome

AF:

0.729

AC:

1064305

AN:

1460550

Hom.:

392977

Cov.:

AF XY:

0.726

AC XY:

527850

AN XY:

726660

show subpopulations

Gnomad4 AFR exome

AF:

0.279

Gnomad4 AMR exome

AF:

0.820

Gnomad4 ASJ exome

AF:

0.667

Gnomad4 EAS exome

AF:

0.690

Gnomad4 SAS exome

AF:

0.643

Gnomad4 FIN exome

AF:

0.814

Gnomad4 NFE exome

AF:

0.746

Gnomad4 OTH exome

AF:

0.699

GnomAD4 genome

AF:

0.619

AC:

93990

AN:

151908

Hom.:

32198

Cov.:

AF XY:

0.625

AC XY:

46360

AN XY:

74226

show subpopulations

Gnomad4 AFR

AF:

0.301

Gnomad4 AMR

AF:

0.742

Gnomad4 ASJ

AF:

0.677

Gnomad4 EAS

AF:

0.674

Gnomad4 SAS

AF:

0.662

Gnomad4 FIN

AF:

0.826

Gnomad4 NFE

AF:

0.742

Gnomad4 OTH

AF:

0.635

Alfa

AF:

0.671

Hom.:

5927

Asia WGS

AF:

0.668

AC:

2321

AN:

3478

EpiCase

AF:

0.721

EpiControl

AF:

0.723

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

clinical testing

GeneDx

Oct 26, 2019

- -

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

Splicing

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