rs1017448

Positions:

• chr2-223601626-C-T

Variant summary

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

The ENST00000305409.3(SCG2):​c.-15+659G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0998 in 152,144 control chromosomes in the GnomAD database, including 1,932 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 0.10 (1932 hom., cov: 32)
• Consequence: SCG2 ENST00000305409.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.05

Genes affected

SCG2 (HGNC:10575): (secretogranin II) The protein encoded by this gene is a member of the chromogranin/secretogranin family of neuroendocrine secretory proteins. Studies in rodents suggest that the full-length protein, secretogranin II, is involved in the packaging or sorting of peptide hormones and neuropeptides into secretory vesicles. The full-length protein is cleaved to produce the active peptide secretoneurin, which exerts chemotaxic effects on specific cell types, and EM66, whose function is unknown. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.29 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCG2	NM_003469.5	c.-15+659G>A		intron_variant		ENST00000305409.3	NP_003460.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCG2	ENST00000305409.3	c.-15+659G>A		intron_variant		1	NM_003469.5	ENSP00000304133	P1
SCG2	ENST00000421386.1	c.-15+516G>A		intron_variant		3		ENSP00000394702
SCG2	ENST00000433889.1	c.-15+516G>A		intron_variant		4		ENSP00000415468

Frequencies

GnomAD3 genomes AF: 0.0996 AC: 15145 AN: 152026 Hom.: 1917 Cov.: 32

Gnomad AFR AF: 0.294

Gnomad AMI AF: 0.0417

Gnomad AMR AF: 0.0532

Gnomad ASJ AF: 0.0593

Gnomad EAS AF: 0.0312

Gnomad SAS AF: 0.0381

Gnomad FIN AF: 0.00584

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0199

Gnomad OTH AF: 0.0818

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

GnomAD4 genome AF: 0.0998 AC: 15190 AN: 152144 Hom.: 1932 Cov.: 32 AF XY: 0.0987 AC XY: 7343 AN XY: 74398

Gnomad4 AFR AF: 0.294

Gnomad4 AMR AF: 0.0531

Gnomad4 ASJ AF: 0.0593

Gnomad4 EAS AF: 0.0310

Gnomad4 SAS AF: 0.0371

Gnomad4 FIN AF: 0.00584

Gnomad4 NFE AF: 0.0199

Gnomad4 OTH AF: 0.0814

Alfa AF: 0.0444 Hom.: 260

Bravo AF: 0.111

Asia WGS AF: 0.0660 AC: 227 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.36
DANN	Benign	0.17

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: rs1017448; hg19: chr2-224466344;