7-122439843-G-A

Variant names:

• chr7-122439843-G-A
• rs3757536
• NM_017954.11:c.2353-1379C>T

Variant summary

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

The NM_017954.11(CADPS2):​c.2353-1379C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.261 in 151,932 control chromosomes in the GnomAD database, including 5,548 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 (5548 hom., cov: 32)
• Consequence: CADPS2 NM_017954.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.179
• Publications: 9 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]

ENSG00000240499 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.343 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CADPS2	NM_017954.11	MANE Select	c.2353-1379C>T		intron	N/A	NP_060424.9
	CADPS2	NM_001363389.2		c.2353-1379C>T		intron	N/A	NP_001350318.1
	CADPS2	NM_001363390.2		c.2353-1379C>T		intron	N/A	NP_001350319.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CADPS2	ENST00000449022.7	TSL:5 MANE Select	c.2353-1379C>T		intron	N/A	ENSP00000398481.2
	CADPS2	ENST00000412584.6	TSL:1	c.2344-1379C>T		intron	N/A	ENSP00000400401.2
	CADPS2	ENST00000313070.11	TSL:5	c.2035-1379C>T		intron	N/A	ENSP00000325581.8

Frequencies

GnomAD3 genomes AF: 0.261 AC: 39637 AN: 151812 Hom.: 5539 Cov.: 32

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.177

Gnomad AMR AF: 0.344

Gnomad ASJ AF: 0.327

Gnomad EAS AF: 0.356

Gnomad SAS AF: 0.285

Gnomad FIN AF: 0.260

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.294

Gnomad OTH AF: 0.294

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

GnomAD4 genome AF: 0.261 AC: 39653 AN: 151932 Hom.: 5548 Cov.: 32 AF XY: 0.262 AC XY: 19415 AN XY: 74224

African (AFR) AF: 0.156 AC: 6486 AN: 41456

American (AMR) AF: 0.345 AC: 5258 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.327 AC: 1134 AN: 3466

East Asian (EAS) AF: 0.357 AC: 1837 AN: 5152

South Asian (SAS) AF: 0.285 AC: 1376 AN: 4820

European-Finnish (FIN) AF: 0.260 AC: 2744 AN: 10546

Middle Eastern (MID) AF: 0.333 AC: 98 AN: 294

European-Non Finnish (NFE) AF: 0.294 AC: 19947 AN: 67944

Other (OTH) AF: 0.290 AC: 612 AN: 2112

Alfa AF: 0.291 Hom.: 3690

Bravo AF: 0.266

Asia WGS AF: 0.286 AC: 996 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.1
DANN	Benign	0.63
PhyloP100		0.18
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: rs3757536; hg19: chr7-122079897;