Genetic Variant ST3GAL2:p.Leu65Arg (chr16-70398337-A-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_006927.4(ST3GAL2):c.194T>G(p.Leu65Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000645 in 1,613,368 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000064 ( 0 hom. )

Consequence

ST3GAL2
NM_006927.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.47

Variant links:

Genes affected

ST3GAL2 (HGNC:10863): (ST3 beta-galactoside alpha-2,3-sialyltransferase 2) The protein encoded by this gene is a type II membrane protein that catalyzes the transfer of sialic acid from CMP-sialic acid to galactose-containing substrates. The encoded protein is normally found in the Golgi but can be proteolytically processed to a soluble form. This protein, which is a member of glycosyltransferase family 29, can use the same acceptor substrates as does sialyltransferase 4A. [provided by RefSeq, Jul 2008]

ST3GAL2 links:

ENSG00000260111 (HGNC:):

ENSG00000260111 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.040671885).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ST3GAL2	NM_006927.4 link	c.194T>G	p.Leu65Arg	missense_variant	Exon 2 of 7	ENST00000342907.3	NP_008858.1	Q16842A0A024QZA4B3KXG9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ST3GAL2	ENST00000342907.3 link	c.194T>G	p.Leu65Arg	missense_variant	Exon 2 of 7	5	NM_006927.4	ENSP00000345477.2	Q16842
ST3GAL2	ENST00000393640.8 link	c.194T>G	p.Leu65Arg	missense_variant	Exon 1 of 6	1		ENSP00000377257.4	Q16842
ENSG00000260111	ENST00000566960.1 link	n.211-786A>C		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes

AF:

0.0000723

AC:

AN:

152240

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000620

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000883

AC:

AN:

249230

Hom.:

AF XY:

0.000111

AC XY:

AN XY:

134986

show subpopulations

Gnomad AFR exome

AF:

0.0000621

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000556

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000268

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000636

AC:

AN:

1461128

Hom.:

Cov.:

AF XY:

0.0000784

AC XY:

AN XY:

726854

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000777

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000719

Gnomad4 OTH exome

AF:

0.000199

GnomAD4 genome

AF:

0.0000723

AC:

AN:

152240

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.0000965

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000620

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000823

Hom.:

Bravo

AF:

0.0000642

ExAC

AF:

0.0000824

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 24, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.194T>G (p.L65R) alteration is located in exon 2 (coding exon 1) of the ST3GAL2 gene. This alteration results from a T to G substitution at nucleotide position 194, causing the leucine (L) at amino acid position 65 to be replaced by an arginine (R). 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

0.055

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Benign

0.65

DEOGEN2

Benign

0.092

T;T

Eigen

Benign

-0.97

Eigen_PC

Benign

-0.92

FATHMM_MKL

Benign

0.21

LIST_S2

Benign

0.61

.;T

M_CAP

Benign

0.0090

MetaRNN

Benign

0.041

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.90

L;L

PrimateAI

Benign

0.47

PROVEAN

Benign

-0.76

N;N

REVEL

Benign

0.028

Sift

Benign

0.29

T;T

Sift4G

Benign

0.32

T;T

Polyphen

0.0

B;B

Vest4

0.19

MVP

0.082

MPC

0.21

ClinPred

0.014

GERP RS

2.9

Varity_R

0.13

gMVP

0.83

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

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