chr2-177994391-A-G

Position:

• chr2-177994391-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016953.4(PDE11A):​c.1071+19911T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.661 in 152,048 control chromosomes in the GnomAD database, including 35,140 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.66 (35140 hom., cov: 32)
• Consequence: PDE11A NM_016953.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.130

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.756 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDE11A	NM_016953.4	c.1071+19911T>C		intron_variant		ENST00000286063.11
PDE11A	NM_001077197.2	c.321+19911T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDE11A	ENST00000286063.11	c.1071+19911T>C		intron_variant		1	NM_016953.4	P1
PDE11A	ENST00000358450.8	c.321+19911T>C		intron_variant		1
	ENST00000457053.1	n.83+17516T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.661 AC: 100490 AN: 151932 Hom.: 35130 Cov.: 32

Gnomad AFR AF: 0.412

Gnomad AMI AF: 0.563

Gnomad AMR AF: 0.752

Gnomad ASJ AF: 0.716

Gnomad EAS AF: 0.720

Gnomad SAS AF: 0.777

Gnomad FIN AF: 0.794

Gnomad MID AF: 0.674

Gnomad NFE AF: 0.758

Gnomad OTH AF: 0.651

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.661 AC: 100534 AN: 152048 Hom.: 35140 Cov.: 32 AF XY: 0.665 AC XY: 49434 AN XY: 74326

Gnomad4 AFR AF: 0.412

Gnomad4 AMR AF: 0.753

Gnomad4 ASJ AF: 0.716

Gnomad4 EAS AF: 0.720

Gnomad4 SAS AF: 0.777

Gnomad4 FIN AF: 0.794

Gnomad4 NFE AF: 0.758

Gnomad4 OTH AF: 0.652

Alfa AF: 0.716 Hom.: 6568

Bravo AF: 0.644

Asia WGS AF: 0.751 AC: 2613 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.8
DANN	Benign	0.74

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

Other links and lift over

dbSNP: rs744397; hg19: chr2-178859118;