chr10-73802684-A-G

Position:

• chr10-73802684-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_003635.4(NDST2):​c.2516T>C​(p.Met839Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000041 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: 0.0000041 (0 hom.)
• Consequence: NDST2 NM_003635.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.22

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]

ENSG00000272916 (HGNC:):

ACMG classification

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, 0.85

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NDST2	NM_003635.4	c.2516T>C	p.Met839Thr	missense_variant	14/15	ENST00000309979.11	NP_003626.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NDST2	ENST00000309979.11	c.2516T>C	p.Met839Thr	missense_variant	14/15	1	NM_003635.4	ENSP00000310657.6
ENSG00000272916	ENST00000603027.5	n.*31T>C		non_coding_transcript_exon_variant	14/17	2		ENSP00000475031.1
ENSG00000272916	ENST00000603027.5	n.*31T>C		3_prime_UTR_variant	14/17	2		ENSP00000475031.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000410 AC: 6 AN: 1461886 Hom.: 0 Cov.: 34 AF XY: 0.00000275 AC XY: 2 AN XY: 727244

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: 0.00000540

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 28, 2023

The c.2516T>C (p.M839T) alteration is located in exon 14 (coding exon 12) of the NDST2 gene. This alteration results from a T to C substitution at nucleotide position 2516, causing the methionine (M) at amino acid position 839 to be replaced by a threonine (T). 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	0.82
BayesDel_addAF	Pathogenic	0.47	D
BayesDel_noAF	Pathogenic	0.43
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Pathogenic	0.88	D;D;.
Eigen	Pathogenic	1.0
Eigen_PC	Pathogenic	0.95
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.99	D;.;D
M_CAP	Uncertain	0.15	D
MetaRNN	Pathogenic	0.85	D;D;D
MetaSVM	Pathogenic	0.84	D
MutationAssessor	Pathogenic	3.7	H;H;.
PrimateAI	Uncertain	0.67	T
PROVEAN	Pathogenic	-4.5	.;D;D
REVEL	Pathogenic	0.91
Sift	Pathogenic	0.0	.;D;D
Sift4G	Pathogenic	0.0010	D;D;D
Polyphen		0.95	P;P;.
Vest4		0.83
MutPred		0.56		Loss of loop (P = 0.0022);Loss of loop (P = 0.0022);.;
MVP		0.93
MPC		0.37
ClinPred		1.0	D
GERP RS		6.1
Varity_R		0.94
gMVP		0.81

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

Other links and lift over

dbSNP: rs911215781; hg19: chr10-75562442; COSMIC: COSV55214080; COSMIC: COSV55214080;