rs2522843

Variant names:

• chr7-82850406-C-A
• rs2522843
• NM_033026.6:c.13655-3159G>T

Variant summary

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

The NM_033026.6(PCLO):​c.13655-3159G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.39 in 151,904 control chromosomes in the GnomAD database, including 12,683 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 0.39 (12683 hom., cov: 32)
• Consequence: PCLO NM_033026.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.135
• Publications: 4 publications found

Genes affected

PCLO (HGNC:13406): (piccolo presynaptic cytomatrix protein) The protein encoded by this gene is part of the presynaptic cytoskeletal matrix, which is involved in establishing active synaptic zones and in synaptic vesicle trafficking. Variations in this gene have been associated with bipolar disorder and major depressive disorder. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2011]

PCLO Gene-Disease associations (from GenCC):

• pontocerebellar hypoplasia type 3

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.677 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCLO	NM_033026.6	c.13655-3159G>T		intron_variant	Intron 10 of 24	ENST00000333891.14	NP_149015.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCLO	ENST00000333891.14	c.13655-3159G>T		intron_variant	Intron 10 of 24	2	NM_033026.6	ENSP00000334319.8

Frequencies

GnomAD3 genomes AF: 0.390 AC: 59200 AN: 151786 Hom.: 12669 Cov.: 32

Gnomad AFR AF: 0.233

Gnomad AMI AF: 0.422

Gnomad AMR AF: 0.418

Gnomad ASJ AF: 0.394

Gnomad EAS AF: 0.695

Gnomad SAS AF: 0.567

Gnomad FIN AF: 0.473

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.429

Gnomad OTH AF: 0.397

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

GnomAD4 genome AF: 0.390 AC: 59246 AN: 151904 Hom.: 12683 Cov.: 32 AF XY: 0.397 AC XY: 29493 AN XY: 74222

African (AFR) AF: 0.233 AC: 9671 AN: 41426

American (AMR) AF: 0.419 AC: 6386 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.394 AC: 1368 AN: 3468

East Asian (EAS) AF: 0.697 AC: 3587 AN: 5150

South Asian (SAS) AF: 0.568 AC: 2738 AN: 4818

European-Finnish (FIN) AF: 0.473 AC: 4986 AN: 10532

Middle Eastern (MID) AF: 0.412 AC: 121 AN: 294

European-Non Finnish (NFE) AF: 0.429 AC: 29168 AN: 67942

Other (OTH) AF: 0.397 AC: 837 AN: 2106

Alfa AF: 0.395 Hom.: 2615

Bravo AF: 0.377

Asia WGS AF: 0.609 AC: 2114 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	0.55
DANN	Benign	0.34
PhyloP100		0.14
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: rs2522843; hg19: chr7-82479722;