chr2-233034458-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_005383.2(NEU2):​c.544C>T​(p.Arg182Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000396 in 1,614,136 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R182Q) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000042 ( 0 hom. )

Consequence

NEU2
NM_005383.2 missense

Scores

6
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.547
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.2793823).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NEU2NM_005383.2 linkc.544C>T p.Arg182Trp missense_variant Exon 2 of 2 ENST00000233840.3 NP_005374.2 Q9Y3R4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NEU2ENST00000233840.3 linkc.544C>T p.Arg182Trp missense_variant Exon 2 of 2 1 NM_005383.2 ENSP00000233840.3 Q9Y3R4

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152164
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000279
AC:
7
AN:
251248
Hom.:
0
AF XY:
0.0000368
AC XY:
5
AN XY:
135832
show subpopulations
Gnomad AFR exome
AF:
0.000123
Gnomad AMR exome
AF:
0.0000289
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000109
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000176
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000417
AC:
61
AN:
1461854
Hom.:
0
Cov.:
34
AF XY:
0.0000413
AC XY:
30
AN XY:
727236
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000101
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000477
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152282
Hom.:
0
Cov.:
33
AF XY:
0.0000134
AC XY:
1
AN XY:
74472
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000434
Hom.:
0
ExAC
AF:
0.0000247
AC:
3
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jun 07, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.544C>T (p.R182W) alteration is located in exon 2 (coding exon 2) of the NEU2 gene. This alteration results from a C to T substitution at nucleotide position 544, causing the arginine (R) at amino acid position 182 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.22
BayesDel_addAF
Benign
-0.12
T
BayesDel_noAF
Benign
-0.17
CADD
Benign
18
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.54
D
Eigen
Benign
-0.086
Eigen_PC
Benign
-0.21
FATHMM_MKL
Benign
0.27
N
LIST_S2
Benign
0.84
T
M_CAP
Uncertain
0.13
D
MetaRNN
Benign
0.28
T
MetaSVM
Uncertain
0.14
D
MutationAssessor
Uncertain
2.4
M
PrimateAI
Benign
0.29
T
PROVEAN
Benign
-1.9
N
REVEL
Uncertain
0.52
Sift
Benign
0.14
T
Sift4G
Benign
0.12
T
Polyphen
0.94
P
Vest4
0.30
MVP
0.95
MPC
0.20
ClinPred
0.11
T
GERP RS
2.9
Varity_R
0.51
gMVP
0.61

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs144556397; hg19: chr2-233899168; COSMIC: COSV99290754; API