15-92444708-C-G

Variant names:

• chr15-92444708-C-G
• rs2305561
• NM_006011.4:c.621C>G

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_006011.4(ST8SIA2):​c.621C>G​(p.Pro207Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 1,614,126 control chromosomes in the GnomAD database, including 23,940 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 0.24 (6916 hom., cov: 33)
  • Exomes 𝑓: 0.14 (17024 hom.)
• Consequence: ST8SIA2 NM_006011.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.50
• Publications: 21 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BP7: Synonymous conserved (PhyloP=-2.5 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.521 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ST8SIA2	NM_006011.4	c.621C>G	p.Pro207Pro	synonymous_variant	Exon 5 of 6	ENST00000268164.8	NP_006002.1
ST8SIA2	NM_001330416.2	c.558C>G	p.Pro186Pro	synonymous_variant	Exon 4 of 5		NP_001317345.1
ST8SIA2	XM_017022642.2	c.684C>G	p.Pro228Pro	synonymous_variant	Exon 5 of 6		XP_016878131.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ST8SIA2	ENST00000268164.8	c.621C>G	p.Pro207Pro	synonymous_variant	Exon 5 of 6	1	NM_006011.4	ENSP00000268164.3
ST8SIA2	ENST00000539113.5	c.558C>G	p.Pro186Pro	synonymous_variant	Exon 4 of 5	1		ENSP00000437382.1
ST8SIA2	ENST00000555434.1	c.492C>G	p.Pro164Pro	synonymous_variant	Exon 4 of 5	5		ENSP00000450851.1
ST8SIA2	ENST00000556382.1	n.391C>G		non_coding_transcript_exon_variant	Exon 3 of 3	3

Frequencies

GnomAD3 genomes AF: 0.236 AC: 35895 AN: 152124 Hom.: 6891 Cov.: 33

Gnomad AFR AF: 0.526

Gnomad AMI AF: 0.204

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.214

Gnomad EAS AF: 0.0300

Gnomad SAS AF: 0.119

Gnomad FIN AF: 0.0851

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.223

GnomAD2 exomes AF: 0.145 AC: 36542 AN: 251206 AF XY: 0.141

Gnomad AFR exome AF: 0.530

Gnomad AMR exome AF: 0.108

Gnomad ASJ exome AF: 0.216

Gnomad EAS exome AF: 0.0318

Gnomad FIN exome AF: 0.0898

Gnomad NFE exome AF: 0.131

Gnomad OTH exome AF: 0.147

GnomAD4 exome AF: 0.135 AC: 197722 AN: 1461882 Hom.: 17024 Cov.: 32 AF XY: 0.134 AC XY: 97665 AN XY: 727238

African (AFR) AF: 0.549 AC: 18391 AN: 33480

American (AMR) AF: 0.115 AC: 5132 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.214 AC: 5599 AN: 26134

East Asian (EAS) AF: 0.0374 AC: 1486 AN: 39700

South Asian (SAS) AF: 0.121 AC: 10449 AN: 86258

European-Finnish (FIN) AF: 0.0895 AC: 4783 AN: 53414

Middle Eastern (MID) AF: 0.206 AC: 1189 AN: 5768

European-Non Finnish (NFE) AF: 0.127 AC: 141279 AN: 1112008

Other (OTH) AF: 0.156 AC: 9414 AN: 60396

GnomAD4 genome AF: 0.236 AC: 35972 AN: 152244 Hom.: 6916 Cov.: 33 AF XY: 0.230 AC XY: 17138 AN XY: 74454

African (AFR) AF: 0.527 AC: 21869 AN: 41518

American (AMR) AF: 0.154 AC: 2350 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.214 AC: 744 AN: 3470

East Asian (EAS) AF: 0.0303 AC: 157 AN: 5186

South Asian (SAS) AF: 0.119 AC: 574 AN: 4826

European-Finnish (FIN) AF: 0.0851 AC: 904 AN: 10618

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.127 AC: 8650 AN: 68002

Other (OTH) AF: 0.219 AC: 464 AN: 2114

Alfa AF: 0.129 Hom.: 559

Bravo AF: 0.255

Asia WGS AF: 0.106 AC: 368 AN: 3478

EpiCase AF: 0.140

EpiControl AF: 0.136

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	6.1
DANN	Benign	0.66
PhyloP100		-2.5
Mutation Taster		=93/7	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: rs2305561; hg19: chr15-92987938; COSMIC: COSV99184376;