Variant 10-73803218-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_003635.4(NDST2):c.2284C>T(p.Arg762Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000015 in 1,461,886 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: not found (cov: 32)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

NDST2
NM_003635.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.70

Variant links:

Genes affected

NDST2 (HGNC:7681): (N-deacetylase and N-sulfotransferase 2) This gene encodes a member of the N-deacetylase/N-sulfotransferase subfamily of the sulfotransferase 1 proteins. The encoded enzyme has dual functions in processing glucosamine and heparin polymers, including N-deacetylation and N-sulfation. The encoded protein may be localized to the Golgi. [provided by RefSeq, Feb 2009]

NDST2 links:

ENSG00000272916 (HGNC:):

ENSG00000272916 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.841

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NDST2	NM_003635.4 linkuse as main transcript	c.2284C>T	p.Arg762Cys	missense_variant	12/15	ENST00000309979.11	NP_003626.1	P52849-1B4E139

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
NDST2	ENST00000309979.11 linkuse as main transcript	c.2284C>T	p.Arg762Cys	missense_variant	12/15	1	NM_003635.4	ENSP00000310657.6	P52849-1
NDST2	ENST00000299641.8 linkuse as main transcript	c.2284C>T	p.Arg762Cys	missense_variant	10/13	1		ENSP00000299641.5	P52849-1
ENSG00000272916	ENST00000603027.5 linkuse as main transcript	n.2284C>T		non_coding_transcript_exon_variant	12/17	2		ENSP00000475031.1	S4R438
NDST2	ENST00000429742.1 linkuse as main transcript	c.127C>T	p.Arg43Cys	missense_variant	1/3	2		ENSP00000392733.1	H7C032

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000795

AC:

AN:

251488

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135918

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000150

AC:

AN:

1461886

Hom.:

Cov.:

AF XY:

0.0000165

AC XY:

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000171

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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

Jul 25, 2023

The c.2284C>T (p.R762C) alteration is located in exon 12 (coding exon 10) of the NDST2 gene. This alteration results from a C to T substitution at nucleotide position 2284, causing the arginine (R) at amino acid position 762 to be replaced by a cysteine (C). 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

Uncertain

0.39

BayesDel_addAF

Pathogenic

0.34

BayesDel_noAF

Pathogenic

0.26

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Pathogenic

0.93

D;D;.;.

Eigen

Pathogenic

0.97

Eigen_PC

Pathogenic

0.91

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.96

D;.;D;.

M_CAP

Uncertain

0.087

MetaRNN

Pathogenic

0.84

D;D;D;D

MetaSVM

Uncertain

0.15

MutationAssessor

Pathogenic

3.9

H;H;.;.

PrimateAI

Uncertain

0.73

PROVEAN

Pathogenic

-5.8

.;D;D;.

REVEL

Uncertain

0.50

Sift

Pathogenic

0.0

.;D;D;.

Sift4G

Pathogenic

0.0010

D;D;D;.

Polyphen

1.0

D;D;.;.

Vest4

0.90

MutPred

0.70

Gain of catalytic residue at W763 (P = 0.0057);Gain of catalytic residue at W763 (P = 0.0057);.;Gain of catalytic residue at W763 (P = 0.0057);

MVP

0.90

MPC

0.39

ClinPred

0.99

GERP RS

6.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.86

gMVP

0.74

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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