Genetic Variant PMP2:c.*115T>C (chr8-81443283-A-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002677.5(PMP2):c.*115T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 673,562 control chromosomes in the GnomAD database, including 23,679 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.24 ( 5594 hom., cov: 32)

Exomes 𝑓: 0.21 ( 18085 hom. )

Consequence

PMP2
NM_002677.5 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.06

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]

PMP2 links:

ENSG00000253859 (HGNC:):

ENSG00000253859 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 8-81443283-A-G is Benign according to our data. Variant chr8-81443283-A-G is described in ClinVar as [Benign]. Clinvar id is 1278092.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.717 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PMP2	NM_002677.5 link	c.*115T>C		3_prime_UTR_variant	Exon 4 of 4	ENST00000256103.3	NP_002668.1
PMP2	NM_001348381.2 link	c.*158T>C		3_prime_UTR_variant	Exon 3 of 3		NP_001335310.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
PMP2	ENST00000256103 link	c.*115T>C	3_prime_UTR_variant	Exon 4 of 4	1	NM_002677.5	ENSP00000256103.2	P02689
PMP2	ENST00000519260 link	c.*158T>C	3_prime_UTR_variant	Exon 3 of 3	1		ENSP00000429917.1	E5RH45
ENSG00000253859	ENST00000524085.2 link	n.298+3190A>G	intron_variant	Intron 2 of 3	5

Frequencies

GnomAD3 genomes

AF:

0.236

AC:

35911

AN:

151920

Hom.:

5582

Cov.:

show subpopulations

Gnomad AFR

AF:

0.341

Gnomad AMI

AF:

0.0658

Gnomad AMR

AF:

0.273

Gnomad ASJ

AF:

0.154

Gnomad EAS

AF:

0.737

Gnomad SAS

AF:

0.183

Gnomad FIN

AF:

0.0853

Gnomad MID

AF:

0.225

Gnomad NFE

AF:

0.160

Gnomad OTH

AF:

0.242

GnomAD4 exome

AF:

0.212

AC:

110533

AN:

521524

Hom.:

18085

Cov.:

AF XY:

0.208

AC XY:

57925

AN XY:

278948

show subpopulations

Gnomad4 AFR exome

AF:

0.355

Gnomad4 AMR exome

AF:

0.366

Gnomad4 ASJ exome

AF:

0.167

Gnomad4 EAS exome

AF:

0.751

Gnomad4 SAS exome

AF:

0.182

Gnomad4 FIN exome

AF:

0.0938

Gnomad4 NFE exome

AF:

0.161

Gnomad4 OTH exome

AF:

0.213

GnomAD4 genome

AF:

0.237

AC:

35962

AN:

152038

Hom.:

5594

Cov.:

AF XY:

0.233

AC XY:

17343

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.341

Gnomad4 AMR

AF:

0.273

Gnomad4 ASJ

AF:

0.154

Gnomad4 EAS

AF:

0.736

Gnomad4 SAS

AF:

0.183

Gnomad4 FIN

AF:

0.0853

Gnomad4 NFE

AF:

0.160

Gnomad4 OTH

AF:

0.245

Alfa

AF:

0.189

Hom.:

770

Bravo

AF:

0.263

Asia WGS

AF:

0.452

AC:

1570

AN:

3472

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 14, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

DANN

Benign

0.76

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over