rs4777989

Positions:

• chr15-92463510-G-A
• chr15-92463510-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006011.4(ST8SIA2):​c.843-590G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.65 in 152,066 control chromosomes in the GnomAD database, including 32,625 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 0.65 (32625 hom., cov: 32)
• Consequence: ST8SIA2 NM_006011.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.327

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.769 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ST8SIA2	NM_006011.4	c.843-590G>A		intron_variant		ENST00000268164.8	NP_006002.1
ST8SIA2	NM_001330416.2	c.780-590G>A		intron_variant			NP_001317345.1
ST8SIA2	XM_017022642.2	c.906-590G>A		intron_variant			XP_016878131.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ST8SIA2	ENST00000268164.8	c.843-590G>A		intron_variant		1	NM_006011.4	ENSP00000268164.3
ST8SIA2	ENST00000539113.5	c.780-590G>A		intron_variant		1		ENSP00000437382.1
ST8SIA2	ENST00000555434.1	c.714-590G>A		intron_variant		5		ENSP00000450851.1

Frequencies

GnomAD3 genomes AF: 0.650 AC: 98725 AN: 151948 Hom.: 32593 Cov.: 32

Gnomad AFR AF: 0.776

Gnomad AMI AF: 0.489

Gnomad AMR AF: 0.626

Gnomad ASJ AF: 0.481

Gnomad EAS AF: 0.581

Gnomad SAS AF: 0.488

Gnomad FIN AF: 0.695

Gnomad MID AF: 0.630

Gnomad NFE AF: 0.600

Gnomad OTH AF: 0.620

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

GnomAD4 genome AF: 0.650 AC: 98802 AN: 152066 Hom.: 32625 Cov.: 32 AF XY: 0.649 AC XY: 48275 AN XY: 74338

Gnomad4 AFR AF: 0.776

Gnomad4 AMR AF: 0.626

Gnomad4 ASJ AF: 0.481

Gnomad4 EAS AF: 0.581

Gnomad4 SAS AF: 0.486

Gnomad4 FIN AF: 0.695

Gnomad4 NFE AF: 0.600

Gnomad4 OTH AF: 0.616

Alfa AF: 0.596 Hom.: 40422

Bravo AF: 0.652

Asia WGS AF: 0.574 AC: 1995 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.6
DANN	Benign	0.53

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: rs4777989; hg19: chr15-93006740;