NM_017954.11:c.3717+1182G>A

Variant names:

• chr7-122324295-C-T
• rs1899689
• NM_017954.11:c.3717+1182G>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.3717+1182G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.377 in 151,922 control chromosomes in the GnomAD database, including 11,060 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 0.38 (11060 hom., cov: 32)
• Consequence: CADPS2 NM_017954.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0560
• Publications: 18 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.454 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.3717+1182G>A		intron	N/A	NP_060424.9
	CADPS2	NM_001363389.2		c.3753+1182G>A		intron	N/A	NP_001350318.1
	CADPS2	NM_001363390.2		c.3738+1182G>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.3717+1182G>A		intron	N/A	ENSP00000398481.2	Q86UW7-1
	CADPS2	ENST00000412584.6	TSL:1	c.3594+1182G>A		intron	N/A	ENSP00000400401.2	Q86UW7-2
	CADPS2	ENST00000951082.1		c.3735+1182G>A		intron	N/A	ENSP00000621141.1

Frequencies

GnomAD3 genomes AF: 0.377 AC: 57259 AN: 151804 Hom.: 11062 Cov.: 32

Gnomad AFR AF: 0.289

Gnomad AMI AF: 0.438

Gnomad AMR AF: 0.420

Gnomad ASJ AF: 0.432

Gnomad EAS AF: 0.471

Gnomad SAS AF: 0.414

Gnomad FIN AF: 0.418

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.401

Gnomad OTH AF: 0.404

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

GnomAD4 genome AF: 0.377 AC: 57275 AN: 151922 Hom.: 11060 Cov.: 32 AF XY: 0.380 AC XY: 28234 AN XY: 74266

African (AFR) AF: 0.288 AC: 11956 AN: 41460

American (AMR) AF: 0.420 AC: 6417 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.432 AC: 1494 AN: 3462

East Asian (EAS) AF: 0.470 AC: 2426 AN: 5162

South Asian (SAS) AF: 0.413 AC: 1992 AN: 4820

European-Finnish (FIN) AF: 0.418 AC: 4411 AN: 10554

Middle Eastern (MID) AF: 0.432 AC: 127 AN: 294

European-Non Finnish (NFE) AF: 0.401 AC: 27212 AN: 67886

Other (OTH) AF: 0.399 AC: 841 AN: 2110

Alfa AF: 0.393 Hom.: 35902

Bravo AF: 0.376

Asia WGS AF: 0.391 AC: 1364 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.2
DANN	Benign	0.58
PhyloP100		0.056
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: rs1899689; hg19: chr7-121964349;