Variant chr2-177669596-A-G 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.2488-29T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.858 in 1,009,858 control chromosomes in the GnomAD database, including 373,612 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.81 ( 50934 hom., cov: 33)

Exomes 𝑓: 0.87 ( 322678 hom. )

Consequence

PDE11A
NM_016953.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.09

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 -20 ACMG points.

BP4

This place is a probable branch point but likely benign (scored 2 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 2-177669596-A-G is Benign according to our data. Variant chr2-177669596-A-G is described in ClinVar as [Benign]. Clinvar id is 1326997.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.955 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
PDE11A	NM_016953.4 linkuse as main transcript	c.2488-29T>C	intron_variant	ENST00000286063.11	NP_058649.3	Q9HCR9-1
PDE11A	NM_001077197.2 linkuse as main transcript	c.1738-29T>C	intron_variant		NP_001070665.1	Q9HCR9-2
PDE11A	NM_001077358.2 linkuse as main transcript	c.1414-29T>C	intron_variant		NP_001070826.1	Q9HCR9-3
PDE11A	NM_001077196.2 linkuse as main transcript	c.1156-29T>C	intron_variant		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.2488-29T>C		intron_variant		1	NM_016953.4	ENSP00000286063.5		Q9HCR9-1

Frequencies

GnomAD3 genomes

AF:

0.812

AC:

123501

AN:

152112

Hom.:

50903

Cov.:

show subpopulations

Gnomad AFR

AF:

0.659

Gnomad AMI

AF:

0.947

Gnomad AMR

AF:

0.872

Gnomad ASJ

AF:

0.806

Gnomad EAS

AF:

0.978

Gnomad SAS

AF:

0.896

Gnomad FIN

AF:

0.887

Gnomad MID

AF:

0.854

Gnomad NFE

AF:

0.859

Gnomad OTH

AF:

0.816

GnomAD3 exomes

AF:

0.865

AC:

215458

AN:

249004

Hom.:

93864

AF XY:

0.868

AC XY:

116834

AN XY:

134664

show subpopulations

Gnomad AFR exome

AF:

0.650

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:

0.854

Gnomad OTH exome

AF:

0.856

GnomAD4 exome

AF:

0.866

AC:

742557

AN:

857628

Hom.:

322678

Cov.:

AF XY:

0.867

AC XY:

392112

AN XY:

452196

show subpopulations

Gnomad4 AFR exome

AF:

0.653

Gnomad4 AMR exome

AF:

0.913

Gnomad4 ASJ exome

AF:

0.812

Gnomad4 EAS exome

AF:

0.988

Gnomad4 SAS exome

AF:

0.895

Gnomad4 FIN exome

AF:

0.886

Gnomad4 NFE exome

AF:

0.860

Gnomad4 OTH exome

AF:

0.851

GnomAD4 genome

AF:

0.812

AC:

123591

AN:

152230

Hom.:

50934

Cov.:

AF XY:

0.816

AC XY:

60769

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.659

Gnomad4 AMR

AF:

0.873

Gnomad4 ASJ

AF:

0.806

Gnomad4 EAS

AF:

0.977

Gnomad4 SAS

AF:

0.896

Gnomad4 FIN

AF:

0.887

Gnomad4 NFE

AF:

0.859

Gnomad4 OTH

AF:

0.818

Alfa

AF:

0.826

Hom.:

10719

Bravo

AF:

0.801

Asia WGS

AF:

0.912

AC:

3169

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

-0.88

CADD

Benign

1.0

DANN

Benign

0.19

BranchPoint Hunter

2.0

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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