rs2243404

Positions:

• chr5-175796613-G-A

Variant summary

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

The ENST00000359546.8(CPLX2):​c.-340G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 152,508 control chromosomes in the GnomAD database, including 2,771 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 0.19 (2766 hom., cov: 33)
  • Exomes 𝑓: 0.19 (5 hom.)
• Consequence: CPLX2 ENST00000359546.8 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0140

Genes affected

CPLX2 (HGNC:2310): (complexin 2) Proteins encoded by the complexin/synaphin gene family are cytosolic proteins that function in synaptic vesicle exocytosis. These proteins bind syntaxin, part of the SNAP receptor. The protein product of this gene binds to the SNAP receptor complex and disrupts it, allowing transmitter release. Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.229 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CPLX2	NM_006650.4	c.-340G>A		5_prime_UTR_variant	1/5
CPLX2	XM_005265799.2	c.-260G>A		5_prime_UTR_variant	1/4
CPLX2	XM_047416650.1	c.-518G>A		5_prime_UTR_variant	1/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CPLX2	ENST00000359546.8	c.-340G>A		5_prime_UTR_variant	1/5	1		P1
CPLX2	ENST00000506642.5			upstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.187 AC: 28471 AN: 152138 Hom.: 2763 Cov.: 33

Gnomad AFR AF: 0.156

Gnomad AMI AF: 0.156

Gnomad AMR AF: 0.187

Gnomad ASJ AF: 0.168

Gnomad EAS AF: 0.0995

Gnomad SAS AF: 0.241

Gnomad FIN AF: 0.170

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.213

Gnomad OTH AF: 0.189

GnomAD4 exome AF: 0.187 AC: 47 AN: 252 Hom.: 5 Cov.: 0 AF XY: 0.191 AC XY: 36 AN XY: 188

Gnomad4 AFR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.750

Gnomad4 FIN exome AF: 0.100

Gnomad4 NFE exome AF: 0.181

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.187 AC: 28482 AN: 152256 Hom.: 2766 Cov.: 33 AF XY: 0.185 AC XY: 13808 AN XY: 74446

Gnomad4 AFR AF: 0.156

Gnomad4 AMR AF: 0.187

Gnomad4 ASJ AF: 0.168

Gnomad4 EAS AF: 0.100

Gnomad4 SAS AF: 0.241

Gnomad4 FIN AF: 0.170

Gnomad4 NFE AF: 0.213

Gnomad4 OTH AF: 0.187

Alfa AF: 0.205 Hom.: 2634

Bravo AF: 0.183

Asia WGS AF: 0.182 AC: 634 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.5
DANN	Benign	0.60

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2243404; hg19: chr5-175223616;