rs757346984

Variant names:

• chr2-106813153-T-C
• rs757346984
• ENST00000409087.3:c.1390A>G

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP6

The NM_001142352.2(ST6GAL2):​c.1390A>G​(p.Thr464Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000893 in 1,119,758 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 8.9e-7 (0 hom.)
• Consequence: ST6GAL2 NM_001142352.2 missense
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.771
• Publications: 2 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 -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12293714).
• BP6: Variant 2-106813153-T-C is Benign according to our data. Variant chr2-106813153-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2681566.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001142352.2. 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.1319-6204A>G		intron	N/A	NP_001135823.1	Q96JF0-1
	ST6GAL2	NM_001142352.2		c.1390A>G	p.Thr464Ala	missense	Exon 6 of 6	NP_001135824.1	Q96JF0-2
	ST6GAL2	NM_001322362.2		c.1319-6204A>G		intron	N/A	NP_001309291.1	Q96JF0-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ST6GAL2	ENST00000409087.3	TSL:1	c.1390A>G	p.Thr464Ala	missense	Exon 6 of 6	ENSP00000387332.3	Q96JF0-2
	ST6GAL2	ENST00000409382.8	TSL:1 MANE Select	c.1319-6204A>G		intron	N/A	ENSP00000386942.3	Q96JF0-1
	ST6GAL2	ENST00000361686.8	TSL:1	c.1319-6204A>G		intron	N/A	ENSP00000355273.4	Q96JF0-1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.0000344 AC: 1 AN: 29084 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000416

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 8.93e-7 AC: 1 AN: 1119758 Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0 AN XY: 537528

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 23150

American (AMR) AF: 0.00 AC: 0 AN: 9426

Ashkenazi Jewish (ASJ) AF: 0.0000594 AC: 1 AN: 16832

East Asian (EAS) AF: 0.00 AC: 0 AN: 26904

South Asian (SAS) AF: 0.00 AC: 0 AN: 31016

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 26862

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3554

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 936592

Other (OTH) AF: 0.00 AC: 0 AN: 45422

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 31

Alfa AF: 0.0000562 Hom.: 0

ExAC AF: 0.000130 AC: 3

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	EBV-positive nodal T- and NK-cell lymphoma (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	4.4
DANN	Benign	0.16
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.95
FATHMM_MKL	Benign	0.025	N
LIST_S2	Benign	0.18	T
M_CAP	Benign	0.039	D
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.77
PROVEAN	Benign	-0.020	N
REVEL	Benign	0.048
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Vest4		0.11
MVP		0.11
ClinPred		0.084	T
Mutation Taster		=100/0	polymorphism

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: rs757346984; hg19: chr2-107429609; COSMIC: COSV62416005;