chr2-106834138-C-T

Variant names:

• chr2-106834138-C-T
• NM_001142351.2:c.952G>A

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_001142351.2(ST6GAL2):​c.952G>A​(p.Asp318Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ST6GAL2 NM_001142351.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.88
• Publications: 0 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_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.968

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.952G>A	p.Asp318Asn	missense	Exon 3 of 6	NP_001135823.1	Q96JF0-1
	ST6GAL2	NM_001322362.2		c.952G>A	p.Asp318Asn	missense	Exon 3 of 6	NP_001309291.1	Q96JF0-1
	ST6GAL2	NM_032528.3		c.952G>A	p.Asp318Asn	missense	Exon 3 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.952G>A	p.Asp318Asn	missense	Exon 3 of 6	ENSP00000386942.3	Q96JF0-1
	ST6GAL2	ENST00000361686.8	TSL:1	c.952G>A	p.Asp318Asn	missense	Exon 3 of 6	ENSP00000355273.4	Q96JF0-1
	ST6GAL2	ENST00000409087.3	TSL:1	c.952G>A	p.Asp318Asn	missense	Exon 3 of 6	ENSP00000387332.3	Q96JF0-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

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	0.32
BayesDel_addAF	Benign	-0.013	T
BayesDel_noAF	Benign	-0.26
CADD	Pathogenic	29
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.35	T
Eigen	Pathogenic	0.99
Eigen_PC	Pathogenic	0.96
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.033	D
MetaRNN	Pathogenic	0.97	D
MetaSVM	Uncertain	-0.076	T
MutationAssessor	Pathogenic	3.0	M
PhyloP100		7.9
PrimateAI	Uncertain	0.78	T
PROVEAN	Pathogenic	-4.4	D
REVEL	Uncertain	0.57
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.010	D
Polyphen		1.0	D
Vest4		0.87
MutPred		0.92		Loss of phosphorylation at S316 (P = 0.1628)
MVP		0.62
MPC		1.4
ClinPred		1.0	D
GERP RS		6.0
Varity_R		0.45
gMVP		0.90
Mutation Taster		=42/58	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.18		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

hg19: chr2-107450594; COSMIC: COSV62416137; COSMIC: COSV62416137;