rs718764

chr7-122506983-G-T

Variant summary

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

The NM_017954.11(CADPS2):c.1542+6266C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.26 in 151,946 control chromosomes in the GnomAD database, including 5,350 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 0.26 (5350 hom., cov: 32)
• Consequence: CADPS2 NM_017954.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.290

Genes affected

CADPS2 (HGNC:16018): (calcium dependent secretion activator 2) This gene encodes a member of the calcium-dependent activator of secretion (CAPS) protein family, which are calcium binding proteins that regulate the exocytosis of synaptic and dense-core vesicles in neurons and neuroendocrine cells. Mutations in this gene may contribute to autism susceptibility. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2009]

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 = 0.33 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CADPS2	NM_017954.11	c.1542+6266C>A		intron_variant		ENST00000449022.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CADPS2	ENST00000449022.7	c.1542+6266C>A		intron_variant		5	NM_017954.11

Frequencies

GnomAD3 genomes AF: 0.260 AC: 39472 AN: 151830 Hom.: 5340 Cov.: 32

Gnomad AFR AF: 0.183

Gnomad AMI AF: 0.177

Gnomad AMR AF: 0.324

Gnomad ASJ AF: 0.281

Gnomad EAS AF: 0.343

Gnomad SAS AF: 0.242

Gnomad FIN AF: 0.262

Gnomad MID AF: 0.283

Gnomad NFE AF: 0.286

Gnomad OTH AF: 0.288

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

GnomAD4 genome AF: 0.260 AC: 39491 AN: 151946 Hom.: 5350 Cov.: 32 AF XY: 0.259 AC XY: 19260 AN XY: 74258

Gnomad4 AFR AF: 0.182

Gnomad4 AMR AF: 0.324

Gnomad4 ASJ AF: 0.281

Gnomad4 EAS AF: 0.343

Gnomad4 SAS AF: 0.243

Gnomad4 FIN AF: 0.262

Gnomad4 NFE AF: 0.286

Gnomad4 OTH AF: 0.284

Alfa AF: 0.274 Hom.: 724

Bravo AF: 0.265

Asia WGS AF: 0.266 AC: 925 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	2.9
Dann	Benign	0.66

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: rs718764; hg19: chr7-122147037;