rs532046874

Variant summary

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

The NM_002677.5(PMP2):​c.388G>C​(p.Glu130Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 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. E130K) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Consequence

PMP2
NM_002677.5 missense

Scores

1
5
13

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.71
Variant links:
Genes affected
PMP2 (HGNC:9117): (peripheral myelin protein 2) The protein encoded by this gene localizes to myelin sheaths of the peripheral nervous system. The encoded protein can bind both the membrane layers of the sheaths and monomeric lipids, and is thought to provide stability to the sheath. A defect in this gene was shown to be a cause of dominant demyelinating CMT neuropathy. [provided by RefSeq, Jan 2017]

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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=0.29902285).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PMP2NM_002677.5 linkc.388G>C p.Glu130Gln missense_variant Exon 4 of 4 ENST00000256103.3 NP_002668.1
PMP2NM_001348381.2 linkc.*32G>C 3_prime_UTR_variant Exon 3 of 3 NP_001335310.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PMP2ENST00000256103.3 linkc.388G>C p.Glu130Gln missense_variant Exon 4 of 4 1 NM_002677.5 ENSP00000256103.2 P02689
PMP2ENST00000519260 linkc.*32G>C 3_prime_UTR_variant Exon 3 of 3 1 ENSP00000429917.1 E5RH45
ENSG00000253859ENST00000524085.2 linkn.298+3316C>G intron_variant Intron 2 of 3 5

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
27
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.10
BayesDel_addAF
Benign
-0.10
T
BayesDel_noAF
Benign
-0.38
CADD
Benign
21
DANN
Uncertain
1.0
DEOGEN2
Benign
0.088
T
Eigen
Uncertain
0.24
Eigen_PC
Uncertain
0.37
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Benign
0.82
T
M_CAP
Benign
0.013
T
MetaRNN
Benign
0.30
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.0
M
PrimateAI
Uncertain
0.59
T
PROVEAN
Benign
-1.8
N
REVEL
Benign
0.069
Sift
Benign
0.050
D
Sift4G
Benign
0.10
T
Polyphen
0.42
B
Vest4
0.10
MutPred
0.44
Gain of methylation at K131 (P = 0.1407);
MVP
0.72
MPC
0.11
ClinPred
0.90
D
GERP RS
5.3
Varity_R
0.59
gMVP
0.79

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-82355644; API