15-92444708-C-G

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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

GnomAD3 exomes AF: 0.145 AC: 36542 AN: 251206 Hom.: 4199 AF XY: 0.141 AC XY: 19103 AN XY: 135846

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 SAS exome AF: 0.121

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

Gnomad4 AFR exome AF: 0.549

Gnomad4 AMR exome AF: 0.115

Gnomad4 ASJ exome AF: 0.214

Gnomad4 EAS exome AF: 0.0374

Gnomad4 SAS exome AF: 0.121

Gnomad4 FIN exome AF: 0.0895

Gnomad4 NFE exome AF: 0.127

Gnomad4 OTH exome AF: 0.156

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

Gnomad4 AFR AF: 0.527

Gnomad4 AMR AF: 0.154

Gnomad4 ASJ AF: 0.214

Gnomad4 EAS AF: 0.0303

Gnomad4 SAS AF: 0.119

Gnomad4 FIN AF: 0.0851

Gnomad4 NFE AF: 0.127

Gnomad4 OTH AF: 0.219

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

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

LitVar

Other links and lift over

dbSNP: rs2305561; hg19: chr15-92987938; COSMIC: COSV99184376;