chr2-223599259-C-T

Variant names:

• chr2-223599259-C-T
• rs747774922
• NM_003469.5:c.24G>A

Variant summary

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

The NM_003469.5(SCG2):​c.24G>A​(p.Trp8*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000697 in 1,434,890 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: SCG2 NM_003469.5 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00100
• 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.24G>A	p.Trp8*	stop_gained	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.24G>A	p.Trp8*	stop_gained	Exon 2 of 2	ENSP00000304133.2	P13521
	SCG2	ENST00000421386.1	TSL:3	c.24G>A	p.Trp8*	stop_gained	Exon 2 of 2	ENSP00000394702.1	C9JQI2
	SCG2	ENST00000433889.1	TSL:4	c.24G>A	p.Trp8*	stop_gained	Exon 3 of 3	ENSP00000415468.1	C9JDT0

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000411 AC: 1 AN: 243102 AF XY: 0.00000758

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000307

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.97e-7 AC: 1 AN: 1434890 Hom.: 0 Cov.: 31 AF XY: 0.00000141 AC XY: 1 AN XY: 708524

African (AFR) AF: 0.00 AC: 0 AN: 32576

American (AMR) AF: 0.0000234 AC: 1 AN: 42748

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25576

East Asian (EAS) AF: 0.00 AC: 0 AN: 38998

South Asian (SAS) AF: 0.00 AC: 0 AN: 84558

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53074

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5634

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1092692

Other (OTH) AF: 0.00 AC: 0 AN: 59034

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	0.080
CADD	Pathogenic	29
DANN	Uncertain	0.98
Eigen	Uncertain	0.19
Eigen_PC	Benign	-0.15
FATHMM_MKL	Benign	0.15	N
PhyloP100		-0.0010
Vest4		0.63
GERP RS		1.5
Mutation Taster		=56/144	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs747774922; hg19: chr2-224463977;