2-177675565-A-T

Variant names:

• chr2-177675565-A-T
• rs3770016
• NM_016953.4:c.2424-47T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_016953.4(PDE11A):​c.2424-47T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.0 (0 hom., cov: 31)
  • Exomes 𝑓: 7.7e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PDE11A NM_016953.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.37
• Publications: 14 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.25).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE11A	NM_016953.4	c.2424-47T>A		intron_variant	Intron 16 of 19	ENST00000286063.11	NP_058649.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE11A	ENST00000286063.11	c.2424-47T>A		intron_variant	Intron 16 of 19	1	NM_016953.4	ENSP00000286063.5

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 152020 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 7.68e-7 AC: 1 AN: 1302432 Hom.: 0 Cov.: 18 AF XY: 0.00 AC XY: 0 AN XY: 655764

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 30172

American (AMR) AF: 0.00 AC: 0 AN: 43900

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25060

East Asian (EAS) AF: 0.00 AC: 0 AN: 38588

South Asian (SAS) AF: 0.00 AC: 0 AN: 82270

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52986

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5470

European-Non Finnish (NFE) AF: 0.00000103 AC: 1 AN: 968944

Other (OTH) AF: 0.00 AC: 0 AN: 55042

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 152020 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 74242

African (AFR) AF: 0.00 AC: 0 AN: 41348

American (AMR) AF: 0.00 AC: 0 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68018

Other (OTH) AF: 0.00 AC: 0 AN: 2088

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.25
CADD	Benign	14
DANN	Benign	0.82
PhyloP100		1.4
PromoterAI		-0.022	Neutral

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: rs3770016; hg19: chr2-178540293;