Variant 2-106843224-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001142351.2(ST6GAL2):c.754C>G(p.Leu252Val) variant causes a missense change. The variant allele was found at a frequency of 0.000128 in 1,569,290 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00012 ( 1 hom. )

Consequence

ST6GAL2
NM_001142351.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.01

Variant links:

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]

ST6GAL2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.23135209).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ST6GAL2	NM_001142351.2 linkuse as main transcript	c.754C>G	p.Leu252Val	missense_variant	2/6	ENST00000409382.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ST6GAL2	ENST00000409382.8 linkuse as main transcript	c.754C>G	p.Leu252Val	missense_variant	2/6	1	NM_001142351.2	P1	Q96JF0-1
ST6GAL2	ENST00000361686.8 linkuse as main transcript	c.754C>G	p.Leu252Val	missense_variant	2/6	1		P1	Q96JF0-1
ST6GAL2	ENST00000409087.3 linkuse as main transcript	c.754C>G	p.Leu252Val	missense_variant	2/6	1			Q96JF0-2

Frequencies

GnomAD3 genomes

AF:

0.000158

AC:

AN:

152128

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.000157

AC:

AN:

178914

Hom.:

AF XY:

0.000154

AC XY:

AN XY:

97442

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000187

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000116

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000205

Gnomad OTH exome

AF:

0.00106

GnomAD4 exome

AF:

0.000125

AC:

177

AN:

1417162

Hom.:

Cov.:

AF XY:

0.000133

AC XY:

AN XY:

700944

show subpopulations

Gnomad4 AFR exome

AF:

0.0000308

Gnomad4 AMR exome

AF:

0.000213

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000207

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000116

Gnomad4 OTH exome

AF:

0.000324

GnomAD4 genome

AF:

0.000158

AC:

AN:

152128

Hom.:

Cov.:

AF XY:

0.000202

AC XY:

AN XY:

74314

show subpopulations

Gnomad4 AFR

AF:

0.0000724

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000235

Gnomad4 OTH

AF:

0.000957

Alfa

AF:

0.000364

Hom.:

Bravo

AF:

0.000170

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000235

AC:

ExAC

AF:

0.000151

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 12, 2023

The c.754C>G (p.L252V) alteration is located in exon 2 (coding exon 1) of the ST6GAL2 gene. This alteration results from a C to G substitution at nucleotide position 754, causing the leucine (L) at amino acid position 252 to be replaced by a valine (V). 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

0.12

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.41

Cadd

Uncertain

Dann

Uncertain

1.0

DEOGEN2

Benign

0.18

T;T;.

Eigen

Uncertain

0.32

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Uncertain

0.93

M_CAP

Uncertain

0.16

MetaRNN

Benign

0.23

T;T;T

MetaSVM

Benign

-0.79

MutationAssessor

Uncertain

2.6

M;M;M

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.74

PROVEAN

Uncertain

-2.5

N;N;N

REVEL

Benign

0.17

Sift

Uncertain

0.0080

D;D;D

Sift4G

Uncertain

0.011

D;D;D

Polyphen

0.74

P;P;P

Vest4

0.18

MVP

0.40

MPC

1.2

ClinPred

0.15

GERP RS

3.1

Varity_R

0.22

gMVP

0.54

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over