7-122393451-G-C

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6_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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.96

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]

(HGNC:):

ACMG classification

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	UniProt
CADPS2	NM_017954.11	c.2878C>G	p.Gln960Glu	missense_variant	21/30	ENST00000449022.7

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.00137 AC: 208 AN: 152104 Hom.: 1 Cov.: 32

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.: 0 AF XY: 0.00124 AC XY: 167 AN XY: 135130

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.: 1 Cov.: 33 AF XY: 0.000983 AC XY: 715 AN XY: 727094

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.: 1 Cov.: 32 AF XY: 0.00132 AC XY: 98 AN XY: 74428

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.: 0

Bravo AF: 0.000982

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.000247 AC: 1

ESP6500EA AF: 0.00179 AC: 15

ExAC AF: 0.00115 AC: 139

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00131

EpiControl AF: 0.000830

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jun 23, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.48
Cadd	Uncertain	23
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	D
LIST_S2	Uncertain	0.90	D;D;D;D;D
M_CAP	Benign	0.0097	T
MetaRNN	Benign	0.0087	T;T;T;T;T
MetaSVM	Benign	-0.99	T
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.58	T
REVEL	Benign	0.12
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	T
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

Other links and lift over

dbSNP: rs199643380; hg19: chr7-122033505;