ENST00000439032.6:n.430G>C

Variant names:

• chr10-62815600-C-G
• rs2297489
• ENST00000439032.6:n.430G>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000439032.6(EGR2):​n.430G>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0578 in 152,320 control chromosomes in the GnomAD database, including 362 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.058 (362 hom., cov: 34)
• Consequence: EGR2 ENST00000439032.6 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.764
• Publications: 3 publications found

Genes affected

EGR2 (HGNC:3239): (early growth response 2) The protein encoded by this gene is a transcription factor with three tandem C2H2-type zinc fingers. Defects in this gene are associated with Charcot-Marie-Tooth disease type 1D (CMT1D), Charcot-Marie-Tooth disease type 4E (CMT4E), and with Dejerine-Sottas syndrome (DSS). Multiple transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Oct 2008]

EGR2 Gene-Disease associations (from GenCC):

• Charcot-Marie-Tooth disease type 4E

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae), G2P
• Charcot-Marie-Tooth disease

  Inheritance: SD Classification: DEFINITIVE Submitted by: ClinGen
• Charcot-Marie-Tooth disease type 1D

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• Charcot-Marie-Tooth disease type 3

  Inheritance: SD, AD Classification: MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet

ENSG00000289487 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant 10-62815600-C-G is Benign according to our data. Variant chr10-62815600-C-G is described in ClinVar as Benign. ClinVar VariationId is 669763.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EGR2	NM_000399.5	c.169+261G>C		intron_variant	Intron 1 of 1	ENST00000242480.4	NP_000390.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EGR2	ENST00000242480.4	c.169+261G>C		intron_variant	Intron 1 of 1	1	NM_000399.5	ENSP00000242480.3

Frequencies

GnomAD3 genomes AF: 0.0577 AC: 8787 AN: 152202 Hom.: 360 Cov.: 34

Gnomad AFR AF: 0.0153

Gnomad AMI AF: 0.124

Gnomad AMR AF: 0.0562

Gnomad ASJ AF: 0.0467

Gnomad EAS AF: 0.200

Gnomad SAS AF: 0.0850

Gnomad FIN AF: 0.0625

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0702

Gnomad OTH AF: 0.0564

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

GnomAD4 genome AF: 0.0578 AC: 8797 AN: 152320 Hom.: 362 Cov.: 34 AF XY: 0.0578 AC XY: 4303 AN XY: 74470

African (AFR) AF: 0.0153 AC: 636 AN: 41588

American (AMR) AF: 0.0560 AC: 858 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0467 AC: 162 AN: 3470

East Asian (EAS) AF: 0.200 AC: 1032 AN: 5160

South Asian (SAS) AF: 0.0853 AC: 412 AN: 4830

European-Finnish (FIN) AF: 0.0625 AC: 663 AN: 10616

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0701 AC: 4770 AN: 68026

Other (OTH) AF: 0.0619 AC: 131 AN: 2116

Alfa AF: 0.0593 Hom.: 34

Bravo AF: 0.0549

Asia WGS AF: 0.142 AC: 492 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 16, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	16
DANN	Benign	0.83
PhyloP100		0.76
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2297489; hg19: chr10-64575360;