rs532046874

Variant names:

• chr8-81443409-C-G
• NM_002677.5:c.388G>C

Your query was ambiguous. Multiple possible variants found:

• chr8-81443409-C-G
• chr8-81443409-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.71

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]

ENSG00000253859 (HGNC:):

ACMG classification

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
PMP2	NM_002677.5	c.388G>C	p.Glu130Gln	missense_variant	Exon 4 of 4	ENST00000256103.3	NP_002668.1
PMP2	NM_001348381.2	c.*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
PMP2	ENST00000256103.3	c.388G>C	p.Glu130Gln	missense_variant	Exon 4 of 4	1	NM_002677.5	ENSP00000256103.2
PMP2	ENST00000519260	c.*32G>C		3_prime_UTR_variant	Exon 3 of 3	1		ENSP00000429917.1
ENSG00000253859	ENST00000524085.2	n.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;