Genetic Variant NM_002523.3:c.202G>C (chr7-98617663-G-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_002523.3(NPTX2):c.202G>C(p.Glu68Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000978 in 1,328,714 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000098 ( 0 hom. )

Consequence

NPTX2
NM_002523.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.21

Publications

0 publications found

Variant links:

Genes affected

NPTX2 (HGNC:7953): (neuronal pentraxin 2) This gene encodes a member of the family of neuronal petraxins, synaptic proteins that are related to C-reactive protein. This protein is involved in excitatory synapse formation. It also plays a role in clustering of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptors at established synapses, resulting in non-apoptotic cell death of dopaminergic nerve cells. Up-regulation of this gene in Parkinson disease (PD) tissues suggests that the protein may be involved in the pathology of PD. [provided by RefSeq, Feb 2009]

NPTX2 links:

ENSG00000306503 (HGNC:):

ENSG00000306503 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002523.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPTX2	NM_002523.3	MANE Select	c.202G>C	p.Glu68Gln	missense	Exon 1 of 5	NP_002514.1	P47972

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NPTX2	ENST00000265634.4	TSL:1 MANE Select	c.202G>C	p.Glu68Gln	missense	Exon 1 of 5	ENSP00000265634.3	P47972
NPTX2	ENST00000903470.1		c.202G>C	p.Glu68Gln	missense	Exon 1 of 5	ENSP00000573529.1
ENSG00000306503	ENST00000819136.1		n.179+1551C>G		intron	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

79190

AF XY:

0.00

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000978

AC:

AN:

1328714

Hom.:

Cov.:

AF XY:

0.00000611

AC XY:

AN XY:

654698

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26586

American (AMR)

AF:

0.00

AC:

AN:

27500

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23194

East Asian (EAS)

AF:

0.0000337

AC:

AN:

29644

South Asian (SAS)

AF:

0.00

AC:

AN:

73232

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32898

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3908

European-Non Finnish (NFE)

AF:

0.0000114

AC:

AN:

1056560

Other (OTH)

AF:

0.00

AC:

AN:

55192

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Benign

-0.016

BayesDel_noAF

Benign

-0.26

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.29

Eigen

Uncertain

0.59

Eigen_PC

Uncertain

0.58

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.87

M_CAP

Uncertain

0.27

MetaRNN

Uncertain

0.64

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

PhyloP100

9.2

PrimateAI

Pathogenic

0.96

PROVEAN

Benign

-0.82

REVEL

Benign

0.22

Sift

Benign

0.52

Sift4G

Benign

0.30

Polyphen

1.0

Vest4

0.68

MutPred

0.27

Gain of MoRF binding (P = 0.0264)

MVP

0.36

MPC

0.49

ClinPred

0.96

GERP RS

4.5

PromoterAI

-0.035

Neutral

(source)

Varity_R

0.41

gMVP

0.60

Mutation Taster

=60/40

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over