ENST00000439032.6:n.*20C>T

Variant names:

• chr10-62815485-G-A
• rs2297488
• ENST00000439032.6:n.*20C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000439032.6(EGR2):​n.*20C>T 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 0.0576 in 152,242 control chromosomes in the GnomAD database, including 365 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.058 (365 hom., cov: 33)
• Consequence: EGR2 ENST00000439032.6 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.33
• Publications: 6 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• 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+376C>T		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+376C>T		intron_variant	Intron 1 of 1	1	NM_000399.5	ENSP00000242480.3

Frequencies

GnomAD3 genomes AF: 0.0576 AC: 8759 AN: 152124 Hom.: 363 Cov.: 33

Gnomad AFR AF: 0.0153

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.0560

Gnomad ASJ AF: 0.0464

Gnomad EAS AF: 0.200

Gnomad SAS AF: 0.0837

Gnomad FIN AF: 0.0626

Gnomad MID AF: 0.0573

Gnomad NFE AF: 0.0700

Gnomad OTH AF: 0.0550

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

GnomAD4 genome AF: 0.0576 AC: 8769 AN: 152242 Hom.: 365 Cov.: 33 AF XY: 0.0577 AC XY: 4297 AN XY: 74452

African (AFR) AF: 0.0153 AC: 636 AN: 41562

American (AMR) AF: 0.0559 AC: 855 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0464 AC: 161 AN: 3470

East Asian (EAS) AF: 0.200 AC: 1034 AN: 5162

South Asian (SAS) AF: 0.0840 AC: 405 AN: 4822

European-Finnish (FIN) AF: 0.0626 AC: 664 AN: 10608

Middle Eastern (MID) AF: 0.0651 AC: 19 AN: 292

European-Non Finnish (NFE) AF: 0.0699 AC: 4755 AN: 67998

Other (OTH) AF: 0.0606 AC: 128 AN: 2112

Alfa AF: 0.0287 Hom.: 15

Bravo AF: 0.0547

Asia WGS AF: 0.140 AC: 486 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	4.2
DANN	Benign	0.97
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs2297488; hg19: chr10-64575245;