NM_017954.11:c.2878C>G

Variant names:

• chr7-122393451-G-C
• rs199643380
• NM_017954.11:c.2878C>G

Variant summary

Our verdict is Likely benign. The variant received -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. 13/22 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
• Publications: 3 publications found

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]

ENSG00000240499 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -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 VariationId is 727782.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017954.11. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CADPS2	NM_017954.11	MANE Select	c.2878C>G	p.Gln960Glu	missense	Exon 21 of 30	NP_060424.9
	CADPS2	NM_001363389.2		c.2899C>G	p.Gln967Glu	missense	Exon 22 of 32	NP_001350318.1
	CADPS2	NM_001363390.2		c.2899C>G	p.Gln967Glu	missense	Exon 22 of 31	NP_001350319.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CADPS2	ENST00000449022.7	TSL:5 MANE Select	c.2878C>G	p.Gln960Glu	missense	Exon 21 of 30	ENSP00000398481.2	Q86UW7-1
	CADPS2	ENST00000412584.6	TSL:1	c.2860C>G	p.Gln954Glu	missense	Exon 19 of 28	ENSP00000400401.2	Q86UW7-2
	CADPS2	ENST00000951082.1		c.2881C>G	p.Gln961Glu	missense	Exon 20 of 30	ENSP00000621141.1

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

GnomAD2 exomes AF: 0.00118 AC: 295 AN: 249096 AF XY: 0.00124

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 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

African (AFR) AF: 0.0000299 AC: 1 AN: 33474

American (AMR) AF: 0.00121 AC: 54 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00528 AC: 138 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.0000928 AC: 8 AN: 86250

European-Finnish (FIN) AF: 0.000337 AC: 18 AN: 53398

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.000997 AC: 1108 AN: 1111808

Other (OTH) AF: 0.00111 AC: 67 AN: 60372

GnomAD4 genome AF: 0.00137 AC: 208 AN: 152222 Hom.: 1 Cov.: 32 AF XY: 0.00132 AC XY: 98 AN XY: 74428

African (AFR) AF: 0.0000241 AC: 1 AN: 41528

American (AMR) AF: 0.00307 AC: 47 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00461 AC: 16 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.000189 AC: 2 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00209 AC: 142 AN: 68018

Other (OTH) AF: 0.00 AC: 0 AN: 2112

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

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.094
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.0097	T
MetaRNN	Benign	0.0087	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.28	N
PhyloP100		4.0
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	1.1	N
REVEL	Benign	0.12
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0010	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
Mutation Taster		=61/39	polymorphism

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

Other links and lift over

dbSNP: rs199643380; hg19: chr7-122033505;