7-122701095-T-C

Variant summary

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

The NM_017954.11(CADPS2):c.453+35860A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.671 in 151,936 control chromosomes in the GnomAD database, including 34,968 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 0.67 (34968 hom., cov: 31)
• Consequence: CADPS2 NM_017954.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.955

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=-0.75).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.779 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CADPS2	NM_017954.11	c.453+35860A>G		intron_variant		ENST00000449022.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CADPS2	ENST00000449022.7	c.453+35860A>G		intron_variant		5	NM_017954.11
CADPS2	ENST00000412584.6	c.453+35860A>G		intron_variant		1		P1
CADPS2	ENST00000313070.11	c.135+35860A>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.671 AC: 101904 AN: 151818 Hom.: 34974 Cov.: 31

Gnomad AFR AF: 0.510

Gnomad AMI AF: 0.837

Gnomad AMR AF: 0.752

Gnomad ASJ AF: 0.741

Gnomad EAS AF: 0.800

Gnomad SAS AF: 0.706

Gnomad FIN AF: 0.659

Gnomad MID AF: 0.845

Gnomad NFE AF: 0.733

Gnomad OTH AF: 0.697

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

GnomAD4 genome AF: 0.671 AC: 101928 AN: 151936 Hom.: 34968 Cov.: 31 AF XY: 0.672 AC XY: 49876 AN XY: 74250

Gnomad4 AFR AF: 0.509

Gnomad4 AMR AF: 0.752

Gnomad4 ASJ AF: 0.741

Gnomad4 EAS AF: 0.799

Gnomad4 SAS AF: 0.707

Gnomad4 FIN AF: 0.659

Gnomad4 NFE AF: 0.733

Gnomad4 OTH AF: 0.694

Alfa AF: 0.659 Hom.: 4739

Bravo AF: 0.673

Asia WGS AF: 0.735 AC: 2551 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
Cadd	Benign	4.9
Dann	Benign	0.93

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: rs6466832; hg19: chr7-122341149;