Genetic Variant ST8SIA2:p.His231Gln (chr15-92444780-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_006011.4(ST8SIA2):c.693C>G(p.His231Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,756 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

ST8SIA2
NM_006011.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.116

Variant links:

Genes affected

ST8SIA2 (HGNC:10870): (ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 2) The protein encoded by this gene is a type II membrane protein that is thought to catalyze the transfer of sialic acid from CMP-sialic acid to N-linked oligosaccharides and glycoproteins. The encoded protein may be found in the Golgi apparatus and may be involved in the production of polysialic acid, a modulator of the adhesive properties of neural cell adhesion molecule (NCAM1). This protein is a member of glycosyltransferase family 29. [provided by RefSeq, Jul 2008]

ST8SIA2 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.040709674).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ST8SIA2	NM_006011.4 link	c.693C>G	p.His231Gln	missense_variant	Exon 5 of 6	ENST00000268164.8	NP_006002.1	Q92186B2R9U8
ST8SIA2	NM_001330416.2 link	c.630C>G	p.His210Gln	missense_variant	Exon 4 of 5		NP_001317345.1	C6G488B2R9U8Q4VAY9
ST8SIA2	XM_017022642.2 link	c.756C>G	p.His252Gln	missense_variant	Exon 5 of 6		XP_016878131.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ST8SIA2	ENST00000268164.8 link	c.693C>G	p.His231Gln	missense_variant	Exon 5 of 6	1	NM_006011.4	ENSP00000268164.3	Q92186
ST8SIA2	ENST00000539113.5 link	c.630C>G	p.His210Gln	missense_variant	Exon 4 of 5	1		ENSP00000437382.1	C6G488
ST8SIA2	ENST00000555434.1 link	c.564C>G	p.His188Gln	missense_variant	Exon 4 of 5	5		ENSP00000450851.1	G3V2T1
ST8SIA2	ENST00000556382.1 link	n.463C>G		non_coding_transcript_exon_variant	Exon 3 of 3	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251066

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135812

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461756

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727198

show subpopulations

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:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 12, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.693C>G (p.H231Q) alteration is located in exon 5 (coding exon 5) of the ST8SIA2 gene. This alteration results from a C to G substitution at nucleotide position 693, causing the histidine (H) at amino acid position 231 to be replaced by a glutamine (Q). 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

Benign

0.075

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.62

CADD

Benign

9.3

DANN

Benign

0.89

DEOGEN2

Benign

0.066

T;.;.

Eigen

Benign

-0.93

Eigen_PC

Benign

-0.67

FATHMM_MKL

Benign

0.64

LIST_S2

Benign

0.70

T;T;T

M_CAP

Benign

0.0055

MetaRNN

Benign

0.041

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.81

N;.;.

PrimateAI

Benign

0.39

PROVEAN

Benign

0.94

N;N;N

REVEL

Benign

0.035

Sift

Benign

0.40

T;T;T

Sift4G

Benign

0.51

T;T;T

Polyphen

0.0010

B;B;.

Vest4

0.13

MutPred

0.33

Loss of catalytic residue at R229 (P = 0.061);.;.;

MVP

0.12

MPC

0.57

ClinPred

0.048

GERP RS

2.5

Varity_R

0.045

gMVP

0.52

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over