2-106832631-A-T

Variant names:

• chr2-106832631-A-T
• NM_001142351.2:c.1077T>A

Variant summary

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

The NM_001142351.2(ST6GAL2):​c.1077T>A​(p.Ser359Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 0.705

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ST6GAL2	NM_001142351.2	c.1077T>A	p.Ser359Arg	missense_variant	Exon 4 of 6	ENST00000409382.8	NP_001135823.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ST6GAL2	ENST00000409382.8	c.1077T>A	p.Ser359Arg	missense_variant	Exon 4 of 6	1	NM_001142351.2	ENSP00000386942.3
ST6GAL2	ENST00000361686.8	c.1077T>A	p.Ser359Arg	missense_variant	Exon 4 of 6	1		ENSP00000355273.4
ST6GAL2	ENST00000409087.3	c.1077T>A	p.Ser359Arg	missense_variant	Exon 4 of 6	1		ENSP00000387332.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 02, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1077T>A (p.S359R) alteration is located in exon 4 (coding exon 3) of the ST6GAL2 gene. This alteration results from a T to A substitution at nucleotide position 1077, causing the serine (S) at amino acid position 359 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	Pathogenic	0.90
BayesDel_addAF	Benign	-0.041	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.24	T;T;.
Eigen	Uncertain	0.27
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.90	.;D;D
M_CAP	Benign	0.029	D
MetaRNN	Uncertain	0.57	D;D;D
MetaSVM	Benign	-0.94	T
MutationAssessor	Uncertain	2.2	M;M;M
PrimateAI	Uncertain	0.58	T
PROVEAN	Uncertain	-3.4	D;D;D
REVEL	Benign	0.23
Sift	Uncertain	0.0080	D;D;D
Sift4G	Uncertain	0.011	D;D;D
Polyphen		0.76	P;P;D
Vest4		0.64
MutPred		0.55		Gain of methylation at K363 (P = 0.1071);Gain of methylation at K363 (P = 0.1071);Gain of methylation at K363 (P = 0.1071);
MVP		0.54
MPC		1.5
ClinPred		0.97	D
GERP RS		2.6
Varity_R		0.47
gMVP		0.87

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-107449087;