2-177690304-T-C

Variant names:

• chr2-177690304-T-C
• rs4893980
• NM_016953.4:c.2345+7028A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016953.4(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 NM_016953.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.291
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PDE11A	NM_016953.4	c.2345+7028A>G		intron_variant	Intron 15 of 19	ENST00000286063.11	NP_058649.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE11A	ENST00000286063.11	c.2345+7028A>G		intron_variant	Intron 15 of 19	1	NM_016953.4	ENSP00000286063.5

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

African (AFR) AF: 0.351 AC: 14549 AN: 41472

American (AMR) AF: 0.797 AC: 12178 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.844 AC: 2929 AN: 3470

East Asian (EAS) AF: 0.818 AC: 4225 AN: 5166

South Asian (SAS) AF: 0.734 AC: 3537 AN: 4818

European-Finnish (FIN) AF: 0.846 AC: 8939 AN: 10572

Middle Eastern (MID) AF: 0.728 AC: 214 AN: 294

European-Non Finnish (NFE) AF: 0.812 AC: 55218 AN: 68006

Other (OTH) AF: 0.712 AC: 1500 AN: 2108

Alfa AF: 0.790 Hom.: 76786

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
PhyloP100		0.29
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4893980; hg19: chr2-178555032;