chr2-106806809-A-C

Variant names:

• chr2-106806809-A-C
• rs958478679
• NM_001142351.2:c.1459T>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001142351.2(ST6GAL2):​c.1459T>G​(p.Tyr487Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Y487H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ST6GAL2 NM_001142351.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.22
• 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: Uncertain_significance. The variant received 2 ACMG points.

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

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.1459T>G	p.Tyr487Asp	missense	Exon 6 of 6	NP_001135823.1	Q96JF0-1
	ST6GAL2	NM_001322362.2		c.1459T>G	p.Tyr487Asp	missense	Exon 6 of 6	NP_001309291.1	Q96JF0-1
	ST6GAL2	NM_032528.3		c.1459T>G	p.Tyr487Asp	missense	Exon 6 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.1459T>G	p.Tyr487Asp	missense	Exon 6 of 6	ENSP00000386942.3	Q96JF0-1
	ST6GAL2	ENST00000361686.8	TSL:1	c.1459T>G	p.Tyr487Asp	missense	Exon 6 of 6	ENSP00000355273.4	Q96JF0-1
	ST6GAL2	ENST00000868339.1		c.1459T>G	p.Tyr487Asp	missense	Exon 6 of 6	ENSP00000538398.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461892 Hom.: 0 Cov.: 44 AF XY: 0.00 AC XY: 0 AN XY: 727248

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112012

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.10
CADD	Pathogenic	29
DANN	Uncertain	0.99
DEOGEN2	Benign	0.25	T
Eigen	Pathogenic	0.85
Eigen_PC	Pathogenic	0.83
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.047	D
MetaRNN	Uncertain	0.73	D
MetaSVM	Benign	-0.69	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		9.2
PrimateAI	Uncertain	0.70	T
PROVEAN	Pathogenic	-6.7	D
REVEL	Uncertain	0.57
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Polyphen		0.99	D
Vest4		0.62
MutPred		0.69		Loss of methylation at K489 (P = 0.064)
MVP		0.46
MPC		1.9
ClinPred		1.0	D
GERP RS		5.8
Varity_R		0.89
gMVP		0.86
Mutation Taster		=26/74	disease causing

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

Other links and lift over

dbSNP: rs958478679; hg19: chr2-107423265;