chr7-122731653-A-G

Variant names:

• chr7-122731653-A-G
• rs9969220
• NM_017954.11:c.453+5302T>C

Variant summary

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

The NM_017954.11(CADPS2):​c.453+5302T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.348 in 146,214 control chromosomes in the GnomAD database, including 9,369 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 0.35 (9369 hom., cov: 30)
• Consequence: CADPS2 NM_017954.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.140
• Publications: 3 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]

LOC124901738 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.66 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.453+5302T>C		intron	N/A	NP_060424.9
	CADPS2	NM_001363389.2		c.453+5302T>C		intron	N/A	NP_001350318.1
	CADPS2	NM_001363390.2		c.453+5302T>C		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.453+5302T>C		intron	N/A	ENSP00000398481.2	Q86UW7-1
	CADPS2	ENST00000412584.6	TSL:1	c.453+5302T>C		intron	N/A	ENSP00000400401.2	Q86UW7-2
	CADPS2	ENST00000951082.1		c.453+5302T>C		intron	N/A	ENSP00000621141.1

Frequencies

GnomAD3 genomes AF: 0.348 AC: 50856 AN: 146108 Hom.: 9360 Cov.: 30

Gnomad AFR AF: 0.208

Gnomad AMI AF: 0.412

Gnomad AMR AF: 0.356

Gnomad ASJ AF: 0.418

Gnomad EAS AF: 0.678

Gnomad SAS AF: 0.555

Gnomad FIN AF: 0.427

Gnomad MID AF: 0.393

Gnomad NFE AF: 0.373

Gnomad OTH AF: 0.362

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

GnomAD4 genome AF: 0.348 AC: 50883 AN: 146214 Hom.: 9369 Cov.: 30 AF XY: 0.356 AC XY: 25345 AN XY: 71248

African (AFR) AF: 0.208 AC: 8191 AN: 39398

American (AMR) AF: 0.356 AC: 5139 AN: 14420

Ashkenazi Jewish (ASJ) AF: 0.418 AC: 1416 AN: 3386

East Asian (EAS) AF: 0.679 AC: 3394 AN: 4998

South Asian (SAS) AF: 0.557 AC: 2558 AN: 4594

European-Finnish (FIN) AF: 0.427 AC: 4269 AN: 10000

Middle Eastern (MID) AF: 0.392 AC: 113 AN: 288

European-Non Finnish (NFE) AF: 0.373 AC: 24716 AN: 66238

Other (OTH) AF: 0.360 AC: 719 AN: 1998

Alfa AF: 0.366 Hom.: 15901

Bravo AF: 0.325

Asia WGS AF: 0.527 AC: 1827 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	6.0
DANN	Benign	0.77
PhyloP100		0.14
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: rs9969220; hg19: chr7-122371707;