NM_005383.2:c.167G>A

Variant names:

• chr2-233032838-G-A
• rs376538610
• NM_005383.2:c.167G>A

Variant summary

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

The NM_005383.2(NEU2):​c.167G>A​(p.Arg56Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: NEU2 NM_005383.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.58
• Publications: 0 publications found

Genes affected

NEU2 (HGNC:7759): (neuraminidase 2) This gene belongs to a family of glycohydrolytic enzymes which remove sialic acid residues from glycoproteins and glycolipids. Expression studies in COS7 cells confirmed that this gene encodes a functional sialidase. Its cytosolic localization was demonstrated by cell fractionation experiments. [provided by RefSeq, Jul 2008]

ACMG classification

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_005383.2. 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
	NEU2	NM_005383.2	MANE Select	c.167G>A	p.Arg56Lys	missense	Exon 1 of 2	NP_005374.2	Q9Y3R4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEU2	ENST00000233840.3	TSL:1 MANE Select	c.167G>A	p.Arg56Lys	missense	Exon 1 of 2	ENSP00000233840.3	Q9Y3R4
	NEU2	ENST00000851001.1		c.167G>A	p.Arg56Lys	missense	Exon 2 of 3	ENSP00000521075.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Asia WGS AF: 0.000289 AC: 1 AN: 3478

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	0.17
BayesDel_addAF	Benign	-0.032	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.69	D
Eigen	Benign	-0.036
Eigen_PC	Benign	-0.017
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.67	T
M_CAP	Uncertain	0.098	D
MetaRNN	Uncertain	0.51	D
MetaSVM	Uncertain	0.17	D
MutationAssessor	Benign	1.9	M
PhyloP100		3.6
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-2.1	N
REVEL	Uncertain	0.30
Sift	Benign	0.15	T
Sift4G	Benign	0.20	T
Polyphen		0.50	P
Vest4		0.15
MutPred		0.70		Gain of ubiquitination at R56 (P = 0.0185)
MVP		0.89
MPC		0.15
ClinPred		0.81	D
GERP RS		3.8
PromoterAI		0.041	Neutral
Varity_R		0.52
gMVP		0.75
Mutation Taster		=88/12	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: rs376538610; hg19: chr2-233897548;