Variant 10-73802483-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_003635.4(NDST2):c.2620C>T(p.Arg874Trp) variant causes a missense change. The variant allele was found at a frequency of 0.0000694 in 1,613,546 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000069 ( 0 hom. )

Consequence

NDST2
NM_003635.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.72

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NDST2	NM_003635.4 linkuse as main transcript	c.2620C>T	p.Arg874Trp	missense_variant	15/15	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.2620C>T	p.Arg874Trp	missense_variant	15/15	1	NM_003635.4	ENSP00000310657.6	P52849-1
ENSG00000272916	ENST00000603027.5 linkuse as main transcript	n.*232C>T		non_coding_transcript_exon_variant	14/17	2		ENSP00000475031.1	S4R438
ENSG00000272916	ENST00000603027.5 linkuse as main transcript	n.*232C>T		3_prime_UTR_variant	14/17	2		ENSP00000475031.1	S4R438

Frequencies

GnomAD3 genomes

AF:

0.0000723

AC:

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

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:

0.000118

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000716

AC:

AN:

251242

Hom.:

AF XY:

0.0000663

AC XY:

AN XY:

135830

show subpopulations

Gnomad AFR exome

AF:

0.0000616

Gnomad AMR exome

AF:

0.000174

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:

0.0000968

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000691

AC:

101

AN:

1461332

Hom.:

Cov.:

AF XY:

0.0000647

AC XY:

AN XY:

726956

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000201

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000562

Gnomad4 NFE exome

AF:

0.0000701

Gnomad4 OTH exome

AF:

0.000166

GnomAD4 genome

AF:

0.0000723

AC:

AN:

152214

Hom.:

Cov.:

AF XY:

0.0000672

AC XY:

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.000128

ExAC

AF:

0.0000659

AC:

EpiCase

AF:

0.000164

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

Feb 28, 2023

The c.2620C>T (p.R874W) alteration is located in exon 15 (coding exon 13) of the NDST2 gene. This alteration results from a C to T substitution at nucleotide position 2620, causing the arginine (R) at amino acid position 874 to be replaced by a tryptophan (W). 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

0.16

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.20

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.64

D;D

Eigen

Pathogenic

0.75

Eigen_PC

Pathogenic

0.77

FATHMM_MKL

Uncertain

0.97

LIST_S2

Pathogenic

0.99

D;.

M_CAP

Benign

0.038

MetaRNN

Uncertain

0.64

D;D

MetaSVM

Benign

-0.52

MutationAssessor

Uncertain

2.2

M;M

PrimateAI

Benign

0.25

PROVEAN

Pathogenic

-4.5

.;D

REVEL

Uncertain

0.33

Sift

Uncertain

0.0010

.;D

Sift4G

Uncertain

0.0020

D;D

Polyphen

0.99

D;D

Vest4

0.46

MVP

0.82

MPC

0.26

ClinPred

0.60

GERP RS

6.2

Varity_R

0.37

gMVP

0.55

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