rs2305668

Variant names:

• chr15-74850420-T-G
• rs2305668
• NM_005697.5:c.632+94A>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 16 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SCAMP2	NM_005697.5	c.632+94A>C		intron_variant	Intron 6 of 8	ENST00000268099.13	NP_005688.2
SCAMP2	NM_001320778.2	c.761+94A>C		intron_variant	Intron 7 of 9		NP_001307707.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCAMP2	ENST00000268099.13	c.632+94A>C		intron_variant	Intron 6 of 8	1	NM_005697.5	ENSP00000268099.9

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

African (AFR) AF: 0.0580 AC: 1325 AN: 22828

American (AMR) AF: 0.169 AC: 6032 AN: 35618

Ashkenazi Jewish (ASJ) AF: 0.135 AC: 2609 AN: 19388

East Asian (EAS) AF: 0.263 AC: 9696 AN: 36846

South Asian (SAS) AF: 0.145 AC: 9810 AN: 67648

European-Finnish (FIN) AF: 0.186 AC: 9113 AN: 49050

Middle Eastern (MID) AF: 0.0866 AC: 397 AN: 4586

European-Non Finnish (NFE) AF: 0.116 AC: 79642 AN: 686234

Other (OTH) AF: 0.122 AC: 5280 AN: 43374

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

African (AFR) AF: 0.0622 AC: 2579 AN: 41462

American (AMR) AF: 0.149 AC: 2265 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.141 AC: 489 AN: 3472

East Asian (EAS) AF: 0.250 AC: 1281 AN: 5126

South Asian (SAS) AF: 0.142 AC: 684 AN: 4804

European-Finnish (FIN) AF: 0.194 AC: 2050 AN: 10566

Middle Eastern (MID) AF: 0.107 AC: 30 AN: 280

European-Non Finnish (NFE) AF: 0.124 AC: 8422 AN: 67900

Other (OTH) AF: 0.120 AC: 253 AN: 2108

Alfa AF: 0.122 Hom.: 2309

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
PhyloP100		-0.34
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=98/2	polymorphism (auto)

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