2-177690304-T-C

Position:

• chr2-177690304-T-C

Variant summary

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

The ENST00000286063.11(PDE11A):​c.2345+7028A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.684 in 152,094 control chromosomes in the GnomAD database, including 38,912 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 0.68 (38912 hom., cov: 32)
• Consequence: PDE11A ENST00000286063.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.291

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.806 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDE11A	NM_016953.4	c.2345+7028A>G		intron_variant		ENST00000286063.11	NP_058649.3
PDE11A-AS1	NR_136171.1	n.105-8125T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDE11A	ENST00000286063.11	c.2345+7028A>G		intron_variant		1	NM_016953.4	ENSP00000286063	P1
PDE11A-AS1	ENST00000653062.1	n.366-8125T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.684 AC: 104021 AN: 151976 Hom.: 38902 Cov.: 32

Gnomad AFR AF: 0.351

Gnomad AMI AF: 0.846

Gnomad AMR AF: 0.797

Gnomad ASJ AF: 0.844

Gnomad EAS AF: 0.818

Gnomad SAS AF: 0.734

Gnomad FIN AF: 0.846

Gnomad MID AF: 0.734

Gnomad NFE AF: 0.812

Gnomad OTH AF: 0.711

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

GnomAD4 genome AF: 0.684 AC: 104061 AN: 152094 Hom.: 38912 Cov.: 32 AF XY: 0.689 AC XY: 51206 AN XY: 74344

Gnomad4 AFR AF: 0.351

Gnomad4 AMR AF: 0.797

Gnomad4 ASJ AF: 0.844

Gnomad4 EAS AF: 0.818

Gnomad4 SAS AF: 0.734

Gnomad4 FIN AF: 0.846

Gnomad4 NFE AF: 0.812

Gnomad4 OTH AF: 0.712

Alfa AF: 0.774 Hom.: 21404

Bravo AF: 0.671

Asia WGS AF: 0.753 AC: 2619 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.8
DANN	Benign	0.67

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: rs4893980; hg19: chr2-178555032;