Variant 17-76573256-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_006456.3(ST6GALNAC2):c.469G>A(p.Gly157Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000186 in 1,612,862 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

ST6GALNAC2
NM_006456.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.86

Variant links:

Genes affected

ST6GALNAC2 (HGNC:10867): (ST6 N-acetylgalactosaminide alpha-2,6-sialyltransferase 2) ST6GALNAC2 belongs to a family of sialyltransferases that add sialic acids to the nonreducing ends of glycoconjugates. At the cell surface, these modifications have roles in cell-cell and cell-substrate interactions, bacterial adhesion, and protein targeting (Samyn-Petit et al., 2000 [PubMed 10742600]).[supplied by OMIM, Mar 2008]

ST6GALNAC2 links:

SNHG16 (HGNC:44352): (small nucleolar RNA host gene 16)

SNHG16 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.975

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ST6GALNAC2	NM_006456.3 linkuse as main transcript	c.469G>A	p.Gly157Arg	missense_variant	4/9	ENST00000225276.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ST6GALNAC2	ENST00000225276.10 linkuse as main transcript	c.469G>A	p.Gly157Arg	missense_variant	4/9	1	NM_006456.3	P1
SNHG16	ENST00000701062.1 linkuse as main transcript	n.194+11858C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000202

AC:

AN:

248092

Hom.:

AF XY:

0.0000223

AC XY:

AN XY:

134406

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000875

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000178

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000185

AC:

AN:

1460678

Hom.:

Cov.:

AF XY:

0.0000151

AC XY:

AN XY:

726594

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000673

Gnomad4 ASJ exome

AF:

0.0000384

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000198

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152184

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000340

ExAC

AF:

0.0000330

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 29, 2022

The c.469G>A (p.G157R) alteration is located in exon 4 (coding exon 4) of the ST6GALNAC2 gene. This alteration results from a G to A substitution at nucleotide position 469, causing the glycine (G) at amino acid position 157 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

0.87

BayesDel_addAF

Uncertain

0.16

BayesDel_noAF

Pathogenic

0.18

Cadd

Pathogenic

Dann

Pathogenic

1.0

DEOGEN2

Benign

0.33

T;.

Eigen

Pathogenic

0.75

Eigen_PC

Uncertain

0.59

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.97

D;D

M_CAP

Benign

0.070

MetaRNN

Pathogenic

0.97

D;D

MetaSVM

Uncertain

-0.019

MutationAssessor

Pathogenic

4.1

H;.

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.80

PROVEAN

Pathogenic

-8.0

D;.

REVEL

Uncertain

0.64

Sift

Pathogenic

0.0

D;.

Sift4G

Pathogenic

0.0010

D;.

Polyphen

1.0

D;.

Vest4

0.98

MutPred

0.90

Gain of MoRF binding (P = 0.0131);.;

MVP

0.53

MPC

0.74

ClinPred

1.0

GERP RS

4.9

Varity_R

0.94

gMVP

0.94

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