rs200360514

Variant names:

• chr7-122388696-A-T
• rs200360514
• NM_017954.11:c.3051T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_017954.11(CADPS2):​c.3051T>A​(p.Asp1017Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000217 in 1,609,650 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00014 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00023 (0 hom.)
• Consequence: CADPS2 NM_017954.11 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.06
• 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 -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.25799787).

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.3051T>A	p.Asp1017Glu	missense	Exon 23 of 30	NP_060424.9
	CADPS2	NM_001363389.2		c.3072T>A	p.Asp1024Glu	missense	Exon 24 of 32	NP_001350318.1
	CADPS2	NM_001363390.2		c.3072T>A	p.Asp1024Glu	missense	Exon 24 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.3051T>A	p.Asp1017Glu	missense	Exon 23 of 30	ENSP00000398481.2	Q86UW7-1
	CADPS2	ENST00000412584.6	TSL:1	c.2913T>A	p.Asp971Glu	missense	Exon 20 of 28	ENSP00000400401.2	Q86UW7-2
	CADPS2	ENST00000951082.1		c.3054T>A	p.Asp1018Glu	missense	Exon 22 of 30	ENSP00000621141.1

Frequencies

GnomAD3 genomes AF: 0.000138 AC: 21 AN: 152084 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000265

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000769 AC: 19 AN: 246952 AF XY: 0.0000747

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000170

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000226 AC: 329 AN: 1457566 Hom.: 0 Cov.: 31 AF XY: 0.000210 AC XY: 152 AN XY: 724966

African (AFR) AF: 0.0000300 AC: 1 AN: 33378

American (AMR) AF: 0.00 AC: 0 AN: 44436

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25968

East Asian (EAS) AF: 0.00 AC: 0 AN: 39660

South Asian (SAS) AF: 0.00 AC: 0 AN: 85720

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53242

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5742

European-Non Finnish (NFE) AF: 0.000289 AC: 321 AN: 1109272

Other (OTH) AF: 0.000116 AC: 7 AN: 60148

GnomAD4 genome AF: 0.000138 AC: 21 AN: 152084 Hom.: 0 Cov.: 32 AF XY: 0.0000808 AC XY: 6 AN XY: 74288

African (AFR) AF: 0.0000724 AC: 3 AN: 41430

American (AMR) AF: 0.00 AC: 0 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000265 AC: 18 AN: 67982

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.000236 Hom.: 0

Bravo AF: 0.000181

TwinsUK AF: 0.000809 AC: 3

ALSPAC AF: 0.000778 AC: 3

ESP6500AA AF: 0.000526 AC: 2

ESP6500EA AF: 0.000608 AC: 5

ExAC AF: 0.0000994 AC: 12

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.44
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T
Eigen	Benign	0.011
Eigen_PC	Benign	0.034
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		2.1
PrimateAI	Uncertain	0.71	T
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.18
Sift	Benign	0.11	T
Sift4G	Benign	0.096	T
Polyphen		0.63	P
Vest4		0.66
MutPred		0.50		Loss of ubiquitination at K1015 (P = 0.0702)
MVP		0.60
MPC		0.031
ClinPred		0.29	T
GERP RS		1.8
Varity_R		0.23
gMVP		0.40
Mutation Taster		=50/50

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

Other links and lift over

dbSNP: rs200360514; hg19: chr7-122028750;