chr10-73808364-G-T

Position:

• chr10-73808364-G-T

Variant summary

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

The NM_003635.4(NDST2):​c.25C>A​(p.Arg9Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000277 in 1,443,530 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: NDST2 NM_003635.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.28

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-ZSWIM8-AS1 (HGNC:):

ACMG classification

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	c.25C>A	p.Arg9Ser	missense_variant	3/15	ENST00000309979.11	NP_003626.1
NDST2-ZSWIM8-AS1	NR_182656.1	n.818C>A		non_coding_transcript_exon_variant	3/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NDST2	ENST00000309979.11	c.25C>A	p.Arg9Ser	missense_variant	3/15	1	NM_003635.4	ENSP00000310657	P1
NDST2	ENST00000299641.8	c.25C>A	p.Arg9Ser	missense_variant	1/13	1		ENSP00000299641	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000917 AC: 2 AN: 218176 Hom.: 0 AF XY: 0.00000847 AC XY: 1 AN XY: 118112

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: 0.0000207

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000277 AC: 4 AN: 1443530 Hom.: 0 Cov.: 32 AF XY: 0.00000279 AC XY: 2 AN XY: 716286

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000236

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: 0.00000272

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.0000165 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.37
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.070
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.23	T;T;.
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.92	D;.;.
M_CAP	Benign	0.055	D
MetaRNN	Uncertain	0.44	T;T;T
MetaSVM	Benign	-0.88	T
MutationAssessor	Uncertain	2.2	M;M;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-1.2	.;N;.
REVEL	Benign	0.27
Sift	Uncertain	0.0030	.;D;.
Sift4G	Uncertain	0.0090	D;D;.
Polyphen		0.99	D;D;.
Vest4		0.77
MutPred		0.49		Loss of MoRF binding (P = 0.0096);Loss of MoRF binding (P = 0.0096);Loss of MoRF binding (P = 0.0096);
MVP		0.74
MPC		0.60
ClinPred		0.70	D
GERP RS		4.5
Varity_R		0.39
gMVP		0.66

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: rs368488804; hg19: chr10-75568122;