7-122506765-G-A

Variant names:

• chr7-122506765-G-A
• rs718765
• NM_017954.11:c.1542+6484C>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.1542+6484C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.26 in 150,544 control chromosomes in the GnomAD database, including 5,303 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 (5303 hom., cov: 31)
• Consequence: CADPS2 NM_017954.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.191
• Publications: 2 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=-0.55).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.328 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.1542+6484C>T		intron	N/A	NP_060424.9
	CADPS2	NM_001363389.2		c.1542+6484C>T		intron	N/A	NP_001350318.1
	CADPS2	NM_001363390.2		c.1542+6484C>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.1542+6484C>T		intron	N/A	ENSP00000398481.2
	CADPS2	ENST00000412584.6	TSL:1	c.1542+6484C>T		intron	N/A	ENSP00000400401.2
	CADPS2	ENST00000313070.11	TSL:5	c.1224+6484C>T		intron	N/A	ENSP00000325581.8

Frequencies

GnomAD3 genomes AF: 0.260 AC: 39131 AN: 150458 Hom.: 5295 Cov.: 31

Gnomad AFR AF: 0.182

Gnomad AMI AF: 0.175

Gnomad AMR AF: 0.324

Gnomad ASJ AF: 0.281

Gnomad EAS AF: 0.341

Gnomad SAS AF: 0.242

Gnomad FIN AF: 0.265

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.287

Gnomad OTH AF: 0.287

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

GnomAD4 genome AF: 0.260 AC: 39143 AN: 150544 Hom.: 5303 Cov.: 31 AF XY: 0.260 AC XY: 19066 AN XY: 73462

African (AFR) AF: 0.181 AC: 7461 AN: 41164

American (AMR) AF: 0.325 AC: 4907 AN: 15110

Ashkenazi Jewish (ASJ) AF: 0.281 AC: 973 AN: 3458

East Asian (EAS) AF: 0.341 AC: 1751 AN: 5134

South Asian (SAS) AF: 0.243 AC: 1159 AN: 4764

European-Finnish (FIN) AF: 0.265 AC: 2628 AN: 9906

Middle Eastern (MID) AF: 0.285 AC: 82 AN: 288

European-Non Finnish (NFE) AF: 0.287 AC: 19428 AN: 67712

Other (OTH) AF: 0.283 AC: 595 AN: 2100

Alfa AF: 0.271 Hom.: 742

Bravo AF: 0.264

Asia WGS AF: 0.263 AC: 915 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	14
DANN	Benign	0.44
PhyloP100		0.19
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: rs718765; hg19: chr7-122146819;