chr8-81444485-TAAAG-T

Variant names:

• chr8-81444485-TAAAG-T
• rs2129706101
• NM_002677.5:c.348+11_348+14delCTTT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_002677.5(PMP2):​c.348+11_348+14delCTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PMP2 NM_002677.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.279
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• Charcot-Marie-Tooth disease, demyelinating, type 1G

  Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)
• Charcot-Marie-Tooth disease

  Inheritance: AD Classification: MODERATE Submitted by: ClinGen

ENSG00000253374 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 8-81444485-TAAAG-T is Benign according to our data. Variant chr8-81444485-TAAAG-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1557307.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002677.5. 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
	PMP2	NM_002677.5	MANE Select	c.348+11_348+14delCTTT		intron	N/A	NP_002668.1	P02689
	PMP2	NM_001348381.2		c.175+11_175+14delCTTT		intron	N/A	NP_001335310.1	E5RH45

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PMP2	ENST00000256103.3	TSL:1 MANE Select	c.348+11_348+14delCTTT		intron	N/A	ENSP00000256103.2	P02689
	PMP2	ENST00000519260.1	TSL:1	c.175+11_175+14delCTTT		intron	N/A	ENSP00000429917.1	E5RH45
	PMP2	ENST00000910617.1		c.342+17_342+20delCTTT		intron	N/A	ENSP00000580676.1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.28

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

Other links and lift over

dbSNP: rs2129706101; hg19: chr8-82356720;