2-177669596-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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 (★).

• Frequency:
  • Genomes: 𝑓 0.81 (50934 hom., cov: 33)
  • Exomes 𝑓: 0.87 (322678 hom.)
• Consequence: PDE11A NM_016953.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.09

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

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: 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_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.955 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDE11A	NM_016953.4	c.2488-29T>C		intron_variant		ENST00000286063.11
PDE11A	NM_001077196.2	c.1156-29T>C		intron_variant
PDE11A	NM_001077197.2	c.1738-29T>C		intron_variant
PDE11A	NM_001077358.2	c.1414-29T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDE11A	ENST00000286063.11	c.2488-29T>C		intron_variant		1	NM_016953.4	P1
PDE11A-AS1	ENST00000653062.1	n.365+15813A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.812 AC: 123501 AN: 152112 Hom.: 50903 Cov.: 33

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

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.: 11 AF XY: 0.867 AC XY: 392112 AN XY: 452196

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.: 33 AF XY: 0.816 AC XY: 60769 AN XY: 74434

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:1

Revision: criteria provided, single submitter

Submissions by phenotype

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

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

Other links and lift over

dbSNP: rs6433687; hg19: chr2-178534324;