7-122377929-T-G

Variant names:

• chr7-122377929-T-G
• rs2189601
• NM_017954.11:c.3387+1439A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017954.11(CADPS2):​c.3387+1439A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.328 in 151,788 control chromosomes in the GnomAD database, including 8,577 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.33 (8577 hom., cov: 32)
• Consequence: CADPS2 NM_017954.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.71
• Publications: 1 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.573 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CADPS2	NM_017954.11	MANE Select	c.3387+1439A>C		intron	N/A	NP_060424.9
	CADPS2	NM_001363389.2		c.3423+1439A>C		intron	N/A	NP_001350318.1
	CADPS2	NM_001363390.2		c.3408+1439A>C		intron	N/A	NP_001350319.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CADPS2	ENST00000449022.7	TSL:5 MANE Select	c.3387+1439A>C		intron	N/A	ENSP00000398481.2
	CADPS2	ENST00000412584.6	TSL:1	c.3264+1439A>C		intron	N/A	ENSP00000400401.2
	CADPS2	ENST00000313070.11	TSL:5	c.3081+1439A>C		intron	N/A	ENSP00000325581.8

Frequencies

GnomAD3 genomes AF: 0.328 AC: 49798 AN: 151672 Hom.: 8571 Cov.: 32

Gnomad AFR AF: 0.331

Gnomad AMI AF: 0.255

Gnomad AMR AF: 0.369

Gnomad ASJ AF: 0.348

Gnomad EAS AF: 0.590

Gnomad SAS AF: 0.343

Gnomad FIN AF: 0.349

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.294

Gnomad OTH AF: 0.334

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.328 AC: 49850 AN: 151788 Hom.: 8577 Cov.: 32 AF XY: 0.334 AC XY: 24768 AN XY: 74142

African (AFR) AF: 0.331 AC: 13681 AN: 41382

American (AMR) AF: 0.369 AC: 5620 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.348 AC: 1202 AN: 3454

East Asian (EAS) AF: 0.591 AC: 3034 AN: 5136

South Asian (SAS) AF: 0.342 AC: 1648 AN: 4814

European-Finnish (FIN) AF: 0.349 AC: 3666 AN: 10518

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.294 AC: 19959 AN: 67932

Other (OTH) AF: 0.338 AC: 712 AN: 2108

Alfa AF: 0.308 Hom.: 6212

Bravo AF: 0.330

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.86
DANN	Benign	0.63
PhyloP100		-1.7
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2189601; hg19: chr7-122017983;