2-233034708-T-G

Variant names:

• chr2-233034708-T-G
• rs538708272
• NM_005383.2:c.794T>G

Variant summary

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

The NM_005383.2(NEU2):​c.794T>G​(p.Val265Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. V265E) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: NEU2 NM_005383.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.73
• 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.794T>G	p.Val265Gly	missense	Exon 2 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.794T>G	p.Val265Gly	missense	Exon 2 of 2	ENSP00000233840.3	Q9Y3R4
	NEU2	ENST00000851001.1		c.794T>G	p.Val265Gly	missense	Exon 3 of 3	ENSP00000521075.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	0.0088	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.79	D
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.38
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.18	T
M_CAP	Uncertain	0.11	D
MetaRNN	Uncertain	0.58	D
MetaSVM	Uncertain	0.18	D
MutationAssessor	Uncertain	2.8	M
PhyloP100		1.7
PrimateAI	Benign	0.26	T
PROVEAN	Pathogenic	-4.5	D
REVEL	Uncertain	0.35
Sift	Benign	0.16	T
Sift4G	Benign	0.14	T
Polyphen		0.99	D
Vest4		0.52
MutPred		0.23		Loss of stability (P = 0.0787)
MVP		0.90
MPC		0.61
ClinPred		0.50	T
GERP RS		1.1
Varity_R		0.54
gMVP		0.49
Mutation Taster		=62/38	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: rs538708272; hg19: chr2-233899418;