15-92430054-C-T

Variant names:

• chr15-92430054-C-T
• rs2049703868
• NM_006011.4:c.104C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006011.4(ST8SIA2):​c.104C>T​(p.Ser35Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S35W) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ST8SIA2 NM_006011.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.24

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17461857).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ST8SIA2	NM_006011.4	c.104C>T	p.Ser35Leu	missense_variant	Exon 2 of 6	ENST00000268164.8	NP_006002.1
ST8SIA2	XM_017022642.2	c.167C>T	p.Ser56Leu	missense_variant	Exon 2 of 6		XP_016878131.1
ST8SIA2	NM_001330416.2	c.99-4193C>T		intron_variant	Intron 1 of 4		NP_001317345.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ST8SIA2	ENST00000268164.8	c.104C>T	p.Ser35Leu	missense_variant	Exon 2 of 6	1	NM_006011.4	ENSP00000268164.3
ST8SIA2	ENST00000539113.5	c.99-4193C>T		intron_variant	Intron 1 of 4	1		ENSP00000437382.1
ST8SIA2	ENST00000555434.1	c.104C>T	p.Ser35Leu	missense_variant	Exon 2 of 5	5		ENSP00000450851.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 13, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.104C>T (p.S35L) alteration is located in exon 2 (coding exon 2) of the ST8SIA2 gene. This alteration results from a C to T substitution at nucleotide position 104, causing the serine (S) at amino acid position 35 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.019	T
BayesDel_noAF	Benign	-0.27
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.18	T;.
Eigen	Benign	-0.00060
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.82	T;T
M_CAP	Benign	0.0072	T
MetaRNN	Benign	0.17	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.49	N;.
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	0.040	N;N
REVEL	Benign	0.15
Sift	Benign	0.20	T;T
Sift4G	Benign	0.43	T;T
Polyphen		0.67	P;.
Vest4		0.59
MutPred		0.26		Loss of glycosylation at S35 (P = 0.0095);Loss of glycosylation at S35 (P = 0.0095);
MVP		0.17
MPC		0.50
ClinPred		0.43	T
GERP RS		5.5
Varity_R		0.082
gMVP		0.49

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.20		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.20		Position offset: -5

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2049703868; hg19: chr15-92973284;