7-122731653-A-G

Position:

• chr7-122731653-A-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CADPS2	NM_017954.11	c.453+5302T>C		intron_variant		ENST00000449022.7	NP_060424.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CADPS2	ENST00000449022.7	c.453+5302T>C		intron_variant		5	NM_017954.11	ENSP00000398481.2
CADPS2	ENST00000412584.6	c.453+5302T>C		intron_variant		1		ENSP00000400401.2
CADPS2	ENST00000313070.11	c.135+5302T>C		intron_variant		5		ENSP00000325581.8

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

Gnomad4 AFR AF: 0.208

Gnomad4 AMR AF: 0.356

Gnomad4 ASJ AF: 0.418

Gnomad4 EAS AF: 0.679

Gnomad4 SAS AF: 0.557

Gnomad4 FIN AF: 0.427

Gnomad4 NFE AF: 0.373

Gnomad4 OTH AF: 0.360

Alfa AF: 0.369 Hom.: 13633

Bravo AF: 0.325

Asia WGS AF: 0.527 AC: 1827 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	6.0
DANN	Benign	0.77

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

Publications

LitVar

Other links and lift over

dbSNP: rs9969220; hg19: chr7-122371707;