2-106843895-A-G

Variant summary

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

The NM_001142351.2(ST6GAL2):c.83T>C(p.Ile28Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000138 in 1,452,970 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ST6GAL2 NM_001142351.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.54

Genes affected

ST6GAL2 (HGNC:10861): (ST6 beta-galactoside alpha-2,6-sialyltransferase 2) This locus encodes a sialyltransferase. The encoded type II transmembrane protein catalyzes the transfer of sialic acid from CMP to an oligosaccharide substrate. Polymorphisms at this locus may be associated with variations in risperidone response in schizophrenic patients. Alternatively spliced transcript variants have been described. [provided by RefSeq, Jan 2012]

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=0.21480444).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ST6GAL2	NM_001142351.2	c.83T>C	p.Ile28Thr	missense_variant	2/6	ENST00000409382.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ST6GAL2	ENST00000409382.8	c.83T>C	p.Ile28Thr	missense_variant	2/6	1	NM_001142351.2	P1
ST6GAL2	ENST00000361686.8	c.83T>C	p.Ile28Thr	missense_variant	2/6	1		P1
ST6GAL2	ENST00000409087.3	c.83T>C	p.Ile28Thr	missense_variant	2/6	1
ST6GAL2	ENST00000419159.2	c.83T>C	p.Ile28Thr	missense_variant	2/2	4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1452970 Hom.: 0 Cov.: 32 AF XY: 0.00000277 AC XY: 2 AN XY: 722820

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 06, 2022

The c.83T>C (p.I28T) alteration is located in exon 2 (coding exon 1) of the ST6GAL2 gene. This alteration results from a T to C substitution at nucleotide position 83, causing the isoleucine (I) at amino acid position 28 to be replaced by a threonine (T). 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	0.23
BayesDel_addAF	Uncertain	0.055	T
BayesDel_noAF	Benign	-0.16
Cadd	Benign	20
Dann	Benign	0.58
DEOGEN2	Benign	0.067	T;T;.;.
Eigen	Benign	-0.023
Eigen_PC	Benign	0.022
FATHMM_MKL	Benign	0.68	D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.21	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	2.0	M;M;M;.
MutationTaster	Benign	0.97	D;D;D
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-1.3	N;N;N;D
REVEL	Benign	0.26
Sift	Uncertain	0.016	D;D;D;D
Sift4G	Benign	0.17	T;T;T;.
Polyphen		0.55	P;P;P;.
Vest4		0.59
MutPred		0.48		Loss of stability (P = 0.002);Loss of stability (P = 0.002);Loss of stability (P = 0.002);Loss of stability (P = 0.002);
MVP		0.34
MPC		0.67
ClinPred		0.69	D
GERP RS		4.6
Varity_R		0.11
gMVP		0.29

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: rs1677039491; hg19: chr2-107460351;