rs374874543

Variant names:

• chr2-106843224-G-C
• rs374874543
• NM_001142351.2:c.754C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.01
• Publications: 1 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.23135209).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001142351.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ST6GAL2	NM_001142351.2	MANE Select	c.754C>G	p.Leu252Val	missense	Exon 2 of 6	NP_001135823.1	Q96JF0-1
	ST6GAL2	NM_001322362.2		c.754C>G	p.Leu252Val	missense	Exon 2 of 6	NP_001309291.1	Q96JF0-1
	ST6GAL2	NM_032528.3		c.754C>G	p.Leu252Val	missense	Exon 2 of 6	NP_115917.1	Q96JF0-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ST6GAL2	ENST00000409382.8	TSL:1 MANE Select	c.754C>G	p.Leu252Val	missense	Exon 2 of 6	ENSP00000386942.3	Q96JF0-1
	ST6GAL2	ENST00000361686.8	TSL:1	c.754C>G	p.Leu252Val	missense	Exon 2 of 6	ENSP00000355273.4	Q96JF0-1
	ST6GAL2	ENST00000409087.3	TSL:1	c.754C>G	p.Leu252Val	missense	Exon 2 of 6	ENSP00000387332.3	Q96JF0-2

Frequencies

GnomAD3 genomes AF: 0.000158 AC: 24 AN: 152128 Hom.: 0 Cov.: 33

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

GnomAD2 exomes AF: 0.000157 AC: 28 AN: 178914 AF XY: 0.000154

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 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.: 1 Cov.: 31 AF XY: 0.000133 AC XY: 93 AN XY: 700944

African (AFR) AF: 0.0000308 AC: 1 AN: 32422

American (AMR) AF: 0.000213 AC: 8 AN: 37580

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24992

East Asian (EAS) AF: 0.00 AC: 0 AN: 37554

South Asian (SAS) AF: 0.000207 AC: 17 AN: 82192

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49174

Middle Eastern (MID) AF: 0.00107 AC: 6 AN: 5606

European-Non Finnish (NFE) AF: 0.000116 AC: 126 AN: 1089080

Other (OTH) AF: 0.000324 AC: 19 AN: 58562

GnomAD4 genome AF: 0.000158 AC: 24 AN: 152128 Hom.: 0 Cov.: 33 AF XY: 0.000202 AC XY: 15 AN XY: 74314

African (AFR) AF: 0.0000724 AC: 3 AN: 41462

American (AMR) AF: 0.000196 AC: 3 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5148

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.000235 AC: 16 AN: 68000

Other (OTH) AF: 0.000957 AC: 2 AN: 2090

Alfa AF: 0.000364 Hom.: 0

Bravo AF: 0.000170

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000235 AC: 2

ExAC AF: 0.000151 AC: 18

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.41
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.18	T
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.75	T
M_CAP	Uncertain	0.16	D
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-0.79	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		4.0
PrimateAI	Uncertain	0.74	T
PROVEAN	Uncertain	-2.5	N
REVEL	Benign	0.17
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.011	D
Polyphen		0.74	P
Vest4		0.18
MVP		0.40
MPC		1.2
ClinPred		0.15	T
GERP RS		3.1
Varity_R		0.22
gMVP		0.54
Mutation Taster		=83/17	polymorphism

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

Other links and lift over

dbSNP: rs374874543; hg19: chr2-107459680;