chr7-122363912-G-A

Position:

• chr7-122363912-G-A

Variant summary

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

The NM_017954.11(CADPS2):​c.3388-2899C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.356 in 151,892 control chromosomes in the GnomAD database, including 9,924 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 0.36 (9924 hom., cov: 31)
• Consequence: CADPS2 NM_017954.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 = 0.537 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CADPS2	NM_017954.11	c.3388-2899C>T		intron_variant		ENST00000449022.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CADPS2	ENST00000449022.7	c.3388-2899C>T		intron_variant		5	NM_017954.11
	ENST00000630777.2	n.162+9496G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.356 AC: 54033 AN: 151774 Hom.: 9918 Cov.: 31

Gnomad AFR AF: 0.355

Gnomad AMI AF: 0.241

Gnomad AMR AF: 0.397

Gnomad ASJ AF: 0.364

Gnomad EAS AF: 0.553

Gnomad SAS AF: 0.388

Gnomad FIN AF: 0.362

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.331

Gnomad OTH AF: 0.349

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

GnomAD4 genome AF: 0.356 AC: 54086 AN: 151892 Hom.: 9924 Cov.: 31 AF XY: 0.361 AC XY: 26799 AN XY: 74214

Gnomad4 AFR AF: 0.355

Gnomad4 AMR AF: 0.397

Gnomad4 ASJ AF: 0.364

Gnomad4 EAS AF: 0.554

Gnomad4 SAS AF: 0.389

Gnomad4 FIN AF: 0.362

Gnomad4 NFE AF: 0.330

Gnomad4 OTH AF: 0.354

Alfa AF: 0.343 Hom.: 4290

Bravo AF: 0.356

Asia WGS AF: 0.474 AC: 1646 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	3.0
DANN	Benign	0.73

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: rs9641684; hg19: chr7-122003966;