2-106843851-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001142351.2(ST6GAL2):c.127C>T(p.Leu43Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,810 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ST6GAL2 NM_001142351.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.31

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 Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0190624).
• BP6: Variant 2-106843851-G-A is Benign according to our data. Variant chr2-106843851-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2253551.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ST6GAL2	NM_001142351.2	c.127C>T	p.Leu43Phe	missense_variant	2/6	ENST00000409382.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ST6GAL2	ENST00000409382.8	c.127C>T	p.Leu43Phe	missense_variant	2/6	1	NM_001142351.2	P1
ST6GAL2	ENST00000361686.8	c.127C>T	p.Leu43Phe	missense_variant	2/6	1		P1
ST6GAL2	ENST00000409087.3	c.127C>T	p.Leu43Phe	missense_variant	2/6	1
ST6GAL2	ENST00000419159.2			downstream_gene_variant		4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459810 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 726260

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 06, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.050
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
Cadd	Benign	8.6
Dann	Benign	0.86
DEOGEN2	Benign	0.037	T;T;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.25	N
M_CAP	Benign	0.0037	T
MetaRNN	Benign	0.019	T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-1.5	N;N;N
MutationTaster	Benign	0.99	N;N;N
PrimateAI	Benign	0.25	T
PROVEAN	Benign	1.1	N;N;N
REVEL	Benign	0.022
Sift	Benign	0.59	T;T;T
Sift4G	Benign	0.48	T;T;T
Polyphen		0.0	B;B;B
Vest4		0.040
MutPred		0.22		Loss of glycosylation at S42 (P = 0.0814);Loss of glycosylation at S42 (P = 0.0814);Loss of glycosylation at S42 (P = 0.0814);
MVP		0.030
MPC		0.53
ClinPred		0.10	T
GERP RS		-0.62
Varity_R		0.032
gMVP		0.17

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

Publications

LitVar

Other links and lift over

dbSNP: rs1362202326; hg19: chr2-107460307;