rs1294290969

Variant names:

• chr2-223598001-G-A
• rs1294290969
• NM_003469.5:c.1282C>T

Your query was ambiguous. Multiple possible variants found:

• chr2-223598001-G-A
• chr2-223598001-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_003469.5(SCG2):​c.1282C>T​(p.Pro428Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P428T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SCG2 NM_003469.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.40
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003469.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCG2	NM_003469.5	MANE Select	c.1282C>T	p.Pro428Ser	missense	Exon 2 of 2	NP_003460.2	P13521

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCG2	ENST00000305409.3	TSL:1 MANE Select	c.1282C>T	p.Pro428Ser	missense	Exon 2 of 2	ENSP00000304133.2	P13521

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.36	T
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.073
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.033	D
MetaRNN	Uncertain	0.59	D
MetaSVM	Benign	-0.75	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		4.4
PrimateAI	Benign	0.40	T
PROVEAN	Pathogenic	-5.2	D
REVEL	Benign	0.20
Sift	Benign	0.12	T
Sift4G	Benign	0.11	T
Polyphen		0.32	B
Vest4		0.41
MutPred		0.74		Gain of relative solvent accessibility (P = 0.0166)
MVP		0.29
MPC		0.088
ClinPred		0.96	D
GERP RS		4.0
Varity_R		0.19
gMVP		0.46
Mutation Taster		=76/24	polymorphism

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: rs1294290969; hg19: chr2-224462719;