chr7-122377929-T-G

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CADPS2	NM_017954.11	c.3387+1439A>C		intron_variant	Intron 25 of 29	ENST00000449022.7	NP_060424.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CADPS2	ENST00000449022.7	c.3387+1439A>C		intron_variant	Intron 25 of 29	5	NM_017954.11	ENSP00000398481.2

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

Gnomad4 AFR AF: 0.331

Gnomad4 AMR AF: 0.369

Gnomad4 ASJ AF: 0.348

Gnomad4 EAS AF: 0.591

Gnomad4 SAS AF: 0.342

Gnomad4 FIN AF: 0.349

Gnomad4 NFE AF: 0.294

Gnomad4 OTH AF: 0.338

Alfa AF: 0.309 Hom.: 5285

Bravo AF: 0.330

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.86
DANN	Benign	0.63

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

Publications

LitVar

Other links and lift over

dbSNP: rs2189601; hg19: chr7-122017983;