Variant 10-73802471-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.2632C>A(p.Gln878Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000753 in 1,460,936 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

NDST2
NM_003635.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.03

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=0.19072086).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NDST2	NM_003635.4 linkuse as main transcript	c.2632C>A	p.Gln878Lys	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.2632C>A	p.Gln878Lys	missense_variant	15/15	1	NM_003635.4	ENSP00000310657.6	P52849-1
ENSG00000272916	ENST00000603027.5 linkuse as main transcript	n.*244C>A		non_coding_transcript_exon_variant	14/17	2		ENSP00000475031.1	S4R438
ENSG00000272916	ENST00000603027.5 linkuse as main transcript	n.*244C>A		3_prime_UTR_variant	14/17	2		ENSP00000475031.1	S4R438

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000119

AC:

AN:

251256

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135838

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:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000753

AC:

AN:

1460936

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

726772

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:

0.000128

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000247

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

Aug 12, 2021

The c.2632C>A (p.Q878K) alteration is located in exon 15 (coding exon 13) of the NDST2 gene. This alteration results from a C to A substitution at nucleotide position 2632, causing the glutamine (Q) at amino acid position 878 to be replaced by a lysine (K). 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

0.10

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.51

CADD

Uncertain

DANN

Benign

0.97

DEOGEN2

Benign

0.18

T;T

Eigen

Benign

0.060

Eigen_PC

Benign

0.22

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.93

D;.

M_CAP

Benign

0.0084

MetaRNN

Benign

0.19

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.0

M;M

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-1.0

.;N

REVEL

Benign

0.14

Sift

Benign

0.12

.;T

Sift4G

Benign

0.70

T;T

Polyphen

0.098

B;B

Vest4

0.51

MutPred

0.19

Gain of ubiquitination at Q878 (P = 0.0054);Gain of ubiquitination at Q878 (P = 0.0054);

MVP

0.58

MPC

0.070

ClinPred

0.17

GERP RS

5.3

Varity_R

0.40

gMVP

0.53

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