7-122320353-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_017954.11(CADPS2):c.3718-15A>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.373 in 1,574,906 control chromosomes in the GnomAD database, including 111,280 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.36 (10155 hom., cov: 33)
  • Exomes 𝑓: 0.37 (101125 hom.)
• Consequence: CADPS2 NM_017954.11 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.169

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 7-122320353-T-G is Benign according to our data. Variant chr7-122320353-T-G is described in ClinVar as [Benign]. Clinvar id is 1283565.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.451 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CADPS2	NM_017954.11	c.3718-15A>C		splice_polypyrimidine_tract_variant, intron_variant		ENST00000449022.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CADPS2	ENST00000449022.7	c.3718-15A>C		splice_polypyrimidine_tract_variant, intron_variant		5	NM_017954.11

Frequencies

GnomAD3 genomes AF: 0.362 AC: 54963 AN: 151966 Hom.: 10156 Cov.: 33

Gnomad AFR AF: 0.281

Gnomad AMI AF: 0.410

Gnomad AMR AF: 0.409

Gnomad ASJ AF: 0.427

Gnomad EAS AF: 0.467

Gnomad SAS AF: 0.412

Gnomad FIN AF: 0.404

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.377

Gnomad OTH AF: 0.386

GnomAD3 exomes AF: 0.392 AC: 88943 AN: 227126 Hom.: 17704 AF XY: 0.393 AC XY: 48611 AN XY: 123568

Gnomad AFR exome AF: 0.276

Gnomad AMR exome AF: 0.426

Gnomad ASJ exome AF: 0.434

Gnomad EAS exome AF: 0.462

Gnomad SAS exome AF: 0.399

Gnomad FIN exome AF: 0.402

Gnomad NFE exome AF: 0.380

Gnomad OTH exome AF: 0.392

GnomAD4 exome AF: 0.375 AC: 533162 AN: 1422822 Hom.: 101125 Cov.: 32 AF XY: 0.376 AC XY: 265636 AN XY: 706154

Gnomad4 AFR exome AF: 0.273

Gnomad4 AMR exome AF: 0.425

Gnomad4 ASJ exome AF: 0.434

Gnomad4 EAS exome AF: 0.434

Gnomad4 SAS exome AF: 0.399

Gnomad4 FIN exome AF: 0.396

Gnomad4 NFE exome AF: 0.369

Gnomad4 OTH exome AF: 0.385

GnomAD4 genome AF: 0.362 AC: 54981 AN: 152084 Hom.: 10155 Cov.: 33 AF XY: 0.365 AC XY: 27128 AN XY: 74338

Gnomad4 AFR AF: 0.281

Gnomad4 AMR AF: 0.410

Gnomad4 ASJ AF: 0.427

Gnomad4 EAS AF: 0.466

Gnomad4 SAS AF: 0.412

Gnomad4 FIN AF: 0.404

Gnomad4 NFE AF: 0.377

Gnomad4 OTH AF: 0.382

Alfa AF: 0.342 Hom.: 3229

Bravo AF: 0.361

Asia WGS AF: 0.389 AC: 1355 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 09, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	4.3
Dann	Benign	0.39

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: rs1348442; hg19: chr7-121960407; COSMIC: COSV57364906;