chr15-92440492-A-G

Variant names:

• chr15-92440492-A-G
• rs2168351
• NM_006011.4:c.548+1882A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006011.4(ST8SIA2):​c.548+1882A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.34 in 152,070 control chromosomes in the GnomAD database, including 9,829 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 0.34 (9829 hom., cov: 32)
• Consequence: ST8SIA2 NM_006011.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.630
• Publications: 11 publications found

Genes affected

ST8SIA2 (HGNC:10870): (ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 2) The protein encoded by this gene is a type II membrane protein that is thought to catalyze the transfer of sialic acid from CMP-sialic acid to N-linked oligosaccharides and glycoproteins. The encoded protein may be found in the Golgi apparatus and may be involved in the production of polysialic acid, a modulator of the adhesive properties of neural cell adhesion molecule (NCAM1). This protein is a member of glycosyltransferase family 29. [provided by RefSeq, Jul 2008]

ST8SIA2 Gene-Disease associations (from GenCC):

• schizophrenia

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.643 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006011.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ST8SIA2	NM_006011.4	MANE Select	c.548+1882A>G		intron	N/A	NP_006002.1
	ST8SIA2	NM_001330416.2		c.485+1882A>G		intron	N/A	NP_001317345.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ST8SIA2	ENST00000268164.8	TSL:1 MANE Select	c.548+1882A>G		intron	N/A	ENSP00000268164.3
	ST8SIA2	ENST00000539113.5	TSL:1	c.485+1882A>G		intron	N/A	ENSP00000437382.1
	ST8SIA2	ENST00000555434.1	TSL:5	c.419+1882A>G		intron	N/A	ENSP00000450851.1

Frequencies

GnomAD3 genomes AF: 0.340 AC: 51653 AN: 151952 Hom.: 9820 Cov.: 32

Gnomad AFR AF: 0.182

Gnomad AMI AF: 0.198

Gnomad AMR AF: 0.451

Gnomad ASJ AF: 0.335

Gnomad EAS AF: 0.662

Gnomad SAS AF: 0.325

Gnomad FIN AF: 0.390

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.382

Gnomad OTH AF: 0.342

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

GnomAD4 genome AF: 0.340 AC: 51664 AN: 152070 Hom.: 9829 Cov.: 32 AF XY: 0.345 AC XY: 25664 AN XY: 74312

African (AFR) AF: 0.182 AC: 7557 AN: 41498

American (AMR) AF: 0.452 AC: 6900 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.335 AC: 1163 AN: 3472

East Asian (EAS) AF: 0.661 AC: 3411 AN: 5158

South Asian (SAS) AF: 0.325 AC: 1560 AN: 4804

European-Finnish (FIN) AF: 0.390 AC: 4128 AN: 10586

Middle Eastern (MID) AF: 0.323 AC: 95 AN: 294

European-Non Finnish (NFE) AF: 0.382 AC: 25951 AN: 67954

Other (OTH) AF: 0.340 AC: 719 AN: 2112

Alfa AF: 0.367 Hom.: 33298

Bravo AF: 0.338

Asia WGS AF: 0.432 AC: 1500 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.8
DANN	Benign	0.65
PhyloP100		0.63
Mutation Taster		=100/0	polymorphism (auto)

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: rs2168351; hg19: chr15-92983722;