chr2-223598961-C-G

Variant names:

• chr2-223598961-C-G
• NM_003469.5:c.322G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003469.5(SCG2):​c.322G>C​(p.Glu108Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,884 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SCG2 NM_003469.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.35

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19248614).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCG2	NM_003469.5	c.322G>C	p.Glu108Gln	missense_variant	Exon 2 of 2	ENST00000305409.3	NP_003460.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCG2	ENST00000305409.3	c.322G>C	p.Glu108Gln	missense_variant	Exon 2 of 2	1	NM_003469.5	ENSP00000304133.2
SCG2	ENST00000421386.1	c.322G>C	p.Glu108Gln	missense_variant	Exon 2 of 2	3		ENSP00000394702.1
SCG2	ENST00000433889.1	c.322G>C	p.Glu108Gln	missense_variant	Exon 3 of 3	4		ENSP00000415468.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461884 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727242

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 26, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.322G>C (p.E108Q) alteration is located in exon 2 (coding exon 1) of the SCG2 gene. This alteration results from a G to C substitution at nucleotide position 322, causing the glutamic acid (E) at amino acid position 108 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	T;.;.
Eigen	Benign	-0.068
Eigen_PC	Benign	0.15
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.73	T;T;T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.19	T;T;T
MetaSVM	Benign	-0.57	T
MutationAssessor	Benign	0.0	N;.;.
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.81	N;N;N
REVEL	Benign	0.16
Sift	Benign	0.041	D;D;D
Sift4G	Benign	0.15	T;D;.
Polyphen		0.11	B;.;.
Vest4		0.15
MutPred		0.51		Gain of MoRF binding (P = 0.0753);Gain of MoRF binding (P = 0.0753);Gain of MoRF binding (P = 0.0753);
MVP		0.19
MPC		0.076
ClinPred		0.57	D
GERP RS		5.5
Varity_R		0.18
gMVP		0.16

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-224463679;