Variant chr10-73803683-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003635.4(NDST2):c.2033C>A(p.Thr678Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,886 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

NDST2
NM_003635.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.55

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14783621).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NDST2	NM_003635.4 linkuse as main transcript	c.2033C>A	p.Thr678Asn	missense_variant	11/15	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.2033C>A	p.Thr678Asn	missense_variant	11/15	1	NM_003635.4	ENSP00000310657.6	P52849-1
NDST2	ENST00000299641.8 linkuse as main transcript	c.2033C>A	p.Thr678Asn	missense_variant	9/13	1		ENSP00000299641.5	P52849-1
ENSG00000272916	ENST00000603027.5 linkuse as main transcript	n.2033C>A		non_coding_transcript_exon_variant	11/17	2		ENSP00000475031.1	S4R438

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461886

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727246

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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 13, 2023

The c.2033C>A (p.T678N) alteration is located in exon 11 (coding exon 9) of the NDST2 gene. This alteration results from a C to A substitution at nucleotide position 2033, causing the threonine (T) at amino acid position 678 to be replaced by an asparagine (N). 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

0.060

BayesDel_addAF

Benign

-0.070

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Benign

0.86

DEOGEN2

Benign

0.30

T;T;.

Eigen

Benign

-0.30

Eigen_PC

Benign

-0.045

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.78

T;.;.

M_CAP

Benign

0.0076

MetaRNN

Benign

0.15

T;T;T

MetaSVM

Benign

-0.73

MutationAssessor

Benign

-0.030

N;N;.

PrimateAI

Uncertain

0.66

PROVEAN

Benign

0.69

.;N;.

REVEL

Benign

0.24

Sift

Benign

1.0

.;T;.

Sift4G

Benign

0.85

T;T;.

Polyphen

0.0

B;B;.

Vest4

0.28

MutPred

0.42

Loss of phosphorylation at T678 (P = 0.0446);Loss of phosphorylation at T678 (P = 0.0446);Loss of phosphorylation at T678 (P = 0.0446);

MVP

0.66

MPC

0.059

ClinPred

0.62

GERP RS

5.0

Varity_R

0.16

gMVP

0.64

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over