7-98617727-G-A

Variant names:

• chr7-98617727-G-A
• rs1041956416
• NM_002523.3:c.266G>A

Variant summary

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

The NM_002523.3(NPTX2):​c.266G>A​(p.Gly89Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000394 in 1,269,596 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: 32)
  • Exomes 𝑓: 0.0000039 (0 hom.)
• Consequence: NPTX2 NM_002523.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.576
• Publications: 0 publications found

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]

ENSG00000306503 (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=0.15726241).

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.266G>A	p.Gly89Asp	missense	Exon 1 of 5	NP_002514.1	P47972

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPTX2	ENST00000265634.4	TSL:1 MANE Select	c.266G>A	p.Gly89Asp	missense	Exon 1 of 5	ENSP00000265634.3	P47972
	NPTX2	ENST00000903470.1		c.266G>A	p.Gly89Asp	missense	Exon 1 of 5	ENSP00000573529.1
	ENSG00000306503	ENST00000819136.1		n.179+1487C>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000394 AC: 5 AN: 1269596 Hom.: 0 Cov.: 31 AF XY: 0.00000644 AC XY: 4 AN XY: 620932

African (AFR) AF: 0.00 AC: 0 AN: 24846

American (AMR) AF: 0.00 AC: 0 AN: 16316

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18604

East Asian (EAS) AF: 0.00 AC: 0 AN: 29090

South Asian (SAS) AF: 0.00 AC: 0 AN: 61518

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30572

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3686

European-Non Finnish (NFE) AF: 0.00000484 AC: 5 AN: 1032404

Other (OTH) AF: 0.00 AC: 0 AN: 52560

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.42	T
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.44
FATHMM_MKL	Benign	0.59	D
LIST_S2	Uncertain	0.88	D
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		0.58
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.054
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.029	D
Polyphen		0.20	B
Vest4		0.29
MutPred		0.17		Loss of ubiquitination at K90 (P = 0.0345)
MVP		0.16
MPC		0.65
ClinPred		0.82	D
GERP RS		2.6
PromoterAI		0.0088	Neutral
Varity_R		0.21
gMVP		0.66
Mutation Taster		=87/13	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: rs1041956416; hg19: chr7-98247039;