7-122387076-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_017954.11(CADPS2):c.3262G>A(p.Asp1088Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00409 in 1,561,438 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0022 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0043 ( 21 hom. )

Consequence

CADPS2
NM_017954.11 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 7.57

Variant links:

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]

CADPS2 links:

ENSG00000240499 (HGNC:):

ENSG00000240499 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.012353718).

BP6

Variant 7-122387076-C-T is Benign according to our data. Variant chr7-122387076-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 715236.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 21 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CADPS2	NM_017954.11 link	c.3262G>A	p.Asp1088Asn	missense_variant	Exon 24 of 30	ENST00000449022.7	NP_060424.9	Q86UW7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CADPS2	ENST00000449022.7 link	c.3262G>A	p.Asp1088Asn	missense_variant	Exon 24 of 30	5	NM_017954.11	ENSP00000398481.2		Q86UW7-1

Frequencies

GnomAD3 genomes

AF:

0.00225

AC:

342

AN:

152070

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000845

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000787

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00418

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.00196

AC:

344

AN:

175128

Hom.:

AF XY:

0.00200

AC XY:

185

AN XY:

92396

show subpopulations

Gnomad AFR exome

AF:

0.000196

Gnomad AMR exome

AF:

0.000649

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000631

Gnomad FIN exome

AF:

0.000113

Gnomad NFE exome

AF:

0.00417

Gnomad OTH exome

AF:

0.00249

GnomAD4 exome

AF:

0.00429

AC:

6044

AN:

1409250

Hom.:

Cov.:

AF XY:

0.00428

AC XY:

2980

AN XY:

695824

show subpopulations

Gnomad4 AFR exome

AF:

0.000619

Gnomad4 AMR exome

AF:

0.000701

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000673

Gnomad4 FIN exome

AF:

0.000460

Gnomad4 NFE exome

AF:

0.00527

Gnomad4 OTH exome

AF:

0.00373

GnomAD4 genome

AF:

0.00225

AC:

342

AN:

152188

Hom.:

Cov.:

AF XY:

0.00192

AC XY:

143

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.000842

Gnomad4 AMR

AF:

0.000786

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.000283

Gnomad4 NFE

AF:

0.00418

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.00359

Hom.:

Bravo

AF:

0.00239

TwinsUK

AF:

0.00620

AC:

ALSPAC

AF:

0.00467

AC:

ESP6500AA

AF:

0.000506

AC:

ESP6500EA

AF:

0.00338

AC:

ExAC

AF:

0.00147

AC:

173

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

CADPS2-related disorder

Benign:1

Feb 01, 2022

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.62

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.40

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.21

T;.;T;.;D

Eigen

Uncertain

0.34

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

0.99

D;D;D;D;D

M_CAP

Benign

0.055

MetaRNN

Benign

0.012

T;T;T;T;T

MetaSVM

Benign

-0.35

MutationAssessor

Uncertain

2.6

.;.;.;.;M

PrimateAI

Uncertain

0.70

PROVEAN

Uncertain

-3.8

.;D;.;D;D

REVEL

Benign

0.26

Sift

Uncertain

0.0020

.;D;.;D;D

Sift4G

Uncertain

0.0040

D;D;D;D;D

Polyphen

1.0

.;.;.;D;D

Vest4

0.86

MVP

0.69

MPC

0.18

ClinPred

0.065

GERP RS

4.9

Varity_R

0.60

gMVP

0.41

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over