rs2305668

Positions:

• chr15-74850420-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005697.5(SCAMP2):​c.632+94A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 1,117,448 control chromosomes in the GnomAD database, including 10,129 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 0.12 (1271 hom., cov: 32)
  • Exomes 𝑓: 0.13 (8858 hom.)
• Consequence: SCAMP2 NM_005697.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.345

Genes affected

SCAMP2 (HGNC:10564): (secretory carrier membrane protein 2) This gene product belongs to the SCAMP family of proteins which are secretory carrier membrane proteins. They function as carriers to the cell surface in post-golgi recycling pathways. Different family members are highly related products of distinct genes, and are usually expressed together. These findings suggest that the SCAMPs may function at the same site during vesicular transport rather than in separate pathways. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Mar 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.239 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SCAMP2	NM_005697.5	c.632+94A>C		intron_variant		ENST00000268099.13
SCAMP2	NM_001320778.2	c.761+94A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCAMP2	ENST00000268099.13	c.632+94A>C		intron_variant		1	NM_005697.5	P1

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18110 AN: 151752 Hom.: 1272 Cov.: 32

Gnomad AFR AF: 0.0624

Gnomad AMI AF: 0.0549

Gnomad AMR AF: 0.149

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.250

Gnomad SAS AF: 0.143

Gnomad FIN AF: 0.194

Gnomad MID AF: 0.113

Gnomad NFE AF: 0.124

Gnomad OTH AF: 0.120

GnomAD4 exome AF: 0.128 AC: 123904 AN: 965572 Hom.: 8858 AF XY: 0.129 AC XY: 63693 AN XY: 494986

Gnomad4 AFR exome AF: 0.0580

Gnomad4 AMR exome AF: 0.169

Gnomad4 ASJ exome AF: 0.135

Gnomad4 EAS exome AF: 0.263

Gnomad4 SAS exome AF: 0.145

Gnomad4 FIN exome AF: 0.186

Gnomad4 NFE exome AF: 0.116

Gnomad4 OTH exome AF: 0.122

GnomAD4 genome AF: 0.119 AC: 18103 AN: 151876 Hom.: 1271 Cov.: 32 AF XY: 0.124 AC XY: 9191 AN XY: 74210

Gnomad4 AFR AF: 0.0622

Gnomad4 AMR AF: 0.149

Gnomad4 ASJ AF: 0.141

Gnomad4 EAS AF: 0.250

Gnomad4 SAS AF: 0.142

Gnomad4 FIN AF: 0.194

Gnomad4 NFE AF: 0.124

Gnomad4 OTH AF: 0.120

Alfa AF: 0.123 Hom.: 1696

Bravo AF: 0.112

Asia WGS AF: 0.156 AC: 544 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.4
DANN	Benign	0.75
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs2305668; hg19: chr15-75142761; COSMIC: COSV51513485; COSMIC: COSV51513485;