Variant 7-122393451-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_017954.11(CADPS2):c.2878C>G(p.Gln960Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000993 in 1,613,842 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0014 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00095 ( 1 hom. )

Consequence

CADPS2
NM_017954.11 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.96

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:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008746475).

BP6

Variant 7-122393451-G-C is Benign according to our data. Variant chr7-122393451-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 727782.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CADPS2	NM_017954.11 linkuse as main transcript	c.2878C>G	p.Gln960Glu	missense_variant	21/30	ENST00000449022.7	NP_060424.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CADPS2	ENST00000449022.7 linkuse as main transcript	c.2878C>G	p.Gln960Glu	missense_variant	21/30	5	NM_017954.11	ENSP00000398481		Q86UW7-1
	ENST00000630777.2 linkuse as main transcript	n.162+39035G>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.00137

AC:

208

AN:

152104

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00308

Gnomad ASJ

AF:

0.00461

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00209

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00118

AC:

295

AN:

249096

Hom.:

AF XY:

0.00124

AC XY:

167

AN XY:

135130

show subpopulations

Gnomad AFR exome

AF:

0.0000646

Gnomad AMR exome

AF:

0.00110

Gnomad ASJ exome

AF:

0.00557

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.000186

Gnomad NFE exome

AF:

0.00165

Gnomad OTH exome

AF:

0.000993

GnomAD4 exome

AF:

0.000954

AC:

1395

AN:

1461620

Hom.:

Cov.:

AF XY:

0.000983

AC XY:

715

AN XY:

727094

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00121

Gnomad4 ASJ exome

AF:

0.00528

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000928

Gnomad4 FIN exome

AF:

0.000337

Gnomad4 NFE exome

AF:

0.000997

Gnomad4 OTH exome

AF:

0.00111

GnomAD4 genome

AF:

0.00137

AC:

208

AN:

152222

Hom.:

Cov.:

AF XY:

0.00132

AC XY:

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00307

Gnomad4 ASJ

AF:

0.00461

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.00209

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00167

Hom.:

Bravo

AF:

0.000982

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.000247

AC:

ESP6500EA

AF:

0.00179

AC:

ExAC

AF:

0.00115

AC:

139

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00131

EpiControl

AF:

0.000830

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jun 23, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.48

CADD

Uncertain

DANN

Benign

0.32

DEOGEN2

Benign

0.0023

T;.;T;.;T

Eigen

Benign

-0.40

Eigen_PC

Benign

-0.094

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.90

D;D;D;D;D

M_CAP

Benign

0.0097

MetaRNN

Benign

0.0087

T;T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.28

.;.;.;.;N

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.58

PROVEAN

Benign

1.1

.;N;.;N;N

REVEL

Benign

0.12

Sift

Benign

1.0

.;T;.;T;T

Sift4G

Benign

1.0

T;T;T;T;T

Polyphen

0.0010, 0.076

.;.;.;B;B

Vest4

0.43

MVP

0.21

MPC

0.023

ClinPred

0.032

GERP RS

5.6

Varity_R

0.086

gMVP

0.27

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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