chr2-223598349-C-A

Variant names:

• chr2-223598349-C-A
• rs1691333408
• NM_003469.5:c.934G>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_003469.5(SCG2):​c.934G>T​(p.Ala312Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000394 in 152,156 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.000039 (0 hom., cov: 32)
• Consequence: SCG2 NM_003469.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.925
• 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.1408312).
• BS2: High AC in GnomAd4 at 6 AD gene.

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.934G>T	p.Ala312Ser	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.934G>T	p.Ala312Ser	missense	Exon 2 of 2	ENSP00000304133.2	P13521

Frequencies

GnomAD3 genomes AF: 0.0000394 AC: 6 AN: 152156 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000956

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.0000394 AC: 6 AN: 152156 Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3 AN XY: 74336

African (AFR) AF: 0.00 AC: 0 AN: 41438

American (AMR) AF: 0.000262 AC: 4 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3462

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68028

Other (OTH) AF: 0.000956 AC: 2 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000264

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	8.7
DANN	Benign	0.34
DEOGEN2	Benign	0.10	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.2
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		0.93
PrimateAI	Benign	0.25	T
PROVEAN	Benign	1.3	N
REVEL	Benign	0.046
Sift	Benign	0.60	T
Sift4G	Benign	0.84	T
Polyphen		0.10	B
Vest4		0.17
MutPred		0.34		Gain of disorder (P = 0.0317)
MVP		0.46
MPC		0.088
ClinPred		0.062	T
GERP RS		-1.4
Varity_R		0.041
gMVP		0.041
Mutation Taster		=95/5	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: rs1691333408; hg19: chr2-224463067;