10-73808190-G-C

Variant names:

• chr10-73808190-G-C
• rs141599100
• NM_003635.4:c.199C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003635.4(NDST2):​c.199C>G​(p.Arg67Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R67Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NDST2 NM_003635.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.42
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• schizophrenia

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ENSG00000272916 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12010768).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003635.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDST2	NM_003635.4	MANE Select	c.199C>G	p.Arg67Gly	missense	Exon 3 of 15	NP_003626.1
	NDST2	NM_001330107.2		c.199C>G	p.Arg67Gly	missense	Exon 3 of 15	NP_001317036.1
	NDST2	NR_160743.1		n.992C>G		non_coding_transcript_exon	Exon 3 of 15

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDST2	ENST00000309979.11	TSL:1 MANE Select	c.199C>G	p.Arg67Gly	missense	Exon 3 of 15	ENSP00000310657.6
	NDST2	ENST00000299641.8	TSL:1	c.199C>G	p.Arg67Gly	missense	Exon 1 of 13	ENSP00000299641.5
	ENSG00000272916	ENST00000603027.5	TSL:2	n.199C>G		non_coding_transcript_exon	Exon 3 of 17	ENSP00000475031.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	13
DANN	Benign	0.96
DEOGEN2	Benign	0.24	T
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.60
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.0	N
PhyloP100		1.4
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.14
Sift	Benign	0.24	T
Sift4G	Benign	0.48	T
Polyphen		0.048	B
Vest4		0.28
MutPred		0.29		Loss of methylation at R67 (P = 0.0106)
MVP		0.39
MPC		0.78
ClinPred		0.10	T
GERP RS		-0.064
Varity_R		0.11
gMVP		0.37
Mutation Taster		=80/20	polymorphism

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

Other links and lift over

dbSNP: rs141599100; hg19: chr10-75567948;