7-122562539-C-T

Variant names:

• chr7-122562539-C-T
• rs2429582
• NM_017954.11:c.1336-7850G>A

Variant summary

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

The NM_017954.11(CADPS2):​c.1336-7850G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.702 in 152,074 control chromosomes in the GnomAD database, including 37,956 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 0.70 (37956 hom., cov: 32)
• Consequence: CADPS2 NM_017954.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.20
• Publications: 14 publications found

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]

ENSG00000293696 (HGNC:):

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 (AFR) allele frequency at 95% confidence interval = 0.808 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017954.11. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CADPS2	NM_017954.11	MANE Select	c.1336-7850G>A		intron	N/A	NP_060424.9
	CADPS2	NM_001363389.2		c.1336-7850G>A		intron	N/A	NP_001350318.1
	CADPS2	NM_001363390.2		c.1336-7850G>A		intron	N/A	NP_001350319.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CADPS2	ENST00000449022.7	TSL:5 MANE Select	c.1336-7850G>A		intron	N/A	ENSP00000398481.2	Q86UW7-1
	CADPS2	ENST00000412584.6	TSL:1	c.1336-7850G>A		intron	N/A	ENSP00000400401.2	Q86UW7-2
	CADPS2	ENST00000951082.1		c.1336-7850G>A		intron	N/A	ENSP00000621141.1

Frequencies

GnomAD3 genomes AF: 0.702 AC: 106673 AN: 151956 Hom.: 37892 Cov.: 32

Gnomad AFR AF: 0.815

Gnomad AMI AF: 0.873

Gnomad AMR AF: 0.693

Gnomad ASJ AF: 0.709

Gnomad EAS AF: 0.695

Gnomad SAS AF: 0.732

Gnomad FIN AF: 0.686

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.635

Gnomad OTH AF: 0.674

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

GnomAD4 genome AF: 0.702 AC: 106792 AN: 152074 Hom.: 37956 Cov.: 32 AF XY: 0.705 AC XY: 52398 AN XY: 74302

African (AFR) AF: 0.815 AC: 33827 AN: 41516

American (AMR) AF: 0.693 AC: 10583 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.709 AC: 2459 AN: 3470

East Asian (EAS) AF: 0.694 AC: 3587 AN: 5166

South Asian (SAS) AF: 0.731 AC: 3520 AN: 4818

European-Finnish (FIN) AF: 0.686 AC: 7250 AN: 10562

Middle Eastern (MID) AF: 0.602 AC: 177 AN: 294

European-Non Finnish (NFE) AF: 0.635 AC: 43164 AN: 67956

Other (OTH) AF: 0.678 AC: 1429 AN: 2108

Alfa AF: 0.656 Hom.: 131996

Bravo AF: 0.708

Asia WGS AF: 0.741 AC: 2575 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.42
DANN	Benign	0.40
PhyloP100		-1.2
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: rs2429582; hg19: chr7-122202593;