10-62813552-T-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000399.5(EGR2):c.1086A>C(p.Arg362Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0282 in 1,606,002 control chromosomes in the GnomAD database, including 1,416 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.046 ( 245 hom., cov: 32)

Exomes 𝑓: 0.026 ( 1171 hom. )

Consequence

EGR2
NM_000399.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts U:2B:7

Conservation

PhyloP100: 0.0450

Publications

8 publications found

Variant links:

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

EGR2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BP6

Variant 10-62813552-T-G is Benign according to our data. Variant chr10-62813552-T-G is described in ClinVar as Benign. ClinVar VariationId is 256013.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.045 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.102 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EGR2	NM_000399.5 link	c.1086A>C	p.Arg362Arg	synonymous_variant	Exon 2 of 2	ENST00000242480.4	NP_000390.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EGR2	ENST00000242480.4 link	c.1086A>C	p.Arg362Arg	synonymous_variant	Exon 2 of 2	1	NM_000399.5	ENSP00000242480.3

Frequencies

GnomAD3 genomes

AF:

0.0463

AC:

6730

AN:

145366

Hom.:

244

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0936

Gnomad AMI

AF:

0.0265

Gnomad AMR

AF:

0.0440

Gnomad ASJ

AF:

0.00180

Gnomad EAS

AF:

0.110

Gnomad SAS

AF:

0.0853

Gnomad FIN

AF:

0.0287

Gnomad MID

AF:

0.0355

Gnomad NFE

AF:

0.0160

Gnomad OTH

AF:

0.0461

GnomAD2 exomes

AF:

0.0404

AC:

10134

AN:

250750

AF XY:

0.0399

show subpopulations

Gnomad AFR exome

AF:

0.0881

Gnomad AMR exome

AF:

0.0654

Gnomad ASJ exome

AF:

0.00198

Gnomad EAS exome

AF:

0.0927

Gnomad FIN exome

AF:

0.0303

Gnomad NFE exome

AF:

0.0154

Gnomad OTH exome

AF:

0.0365

GnomAD4 exome

AF:

0.0263

AC:

38481

AN:

1460516

Hom.:

1171

Cov.:

AF XY:

0.0271

AC XY:

19700

AN XY:

726544

show subpopulations

African (AFR)

AF:

0.0937

AC:

3135

AN:

33470

American (AMR)

AF:

0.0613

AC:

2736

AN:

44658

Ashkenazi Jewish (ASJ)

AF:

0.00203

AC:

AN:

26122

East Asian (EAS)

AF:

0.136

AC:

5383

AN:

39682

South Asian (SAS)

AF:

0.0676

AC:

5818

AN:

86092

European-Finnish (FIN)

AF:

0.0293

AC:

1542

AN:

52556

Middle Eastern (MID)

AF:

0.0414

AC:

239

AN:

5766

European-Non Finnish (NFE)

AF:

0.0157

AC:

17462

AN:

1111802

Other (OTH)

AF:

0.0350

AC:

2113

AN:

60368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

2791

5582

8374

11165

13956

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

850

1700

2550

3400

4250

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0463

AC:

6736

AN:

145486

Hom.:

245

Cov.:

AF XY:

0.0470

AC XY:

3348

AN XY:

71292

show subpopulations

African (AFR)

AF:

0.0935

AC:

3697

AN:

39532

American (AMR)

AF:

0.0439

AC:

652

AN:

14858

Ashkenazi Jewish (ASJ)

AF:

0.00180

AC:

AN:

3340

East Asian (EAS)

AF:

0.110

AC:

529

AN:

4806

South Asian (SAS)

AF:

0.0854

AC:

391

AN:

4578

European-Finnish (FIN)

AF:

0.0287

AC:

296

AN:

10328

Middle Eastern (MID)

AF:

0.0341

AC:

AN:

264

European-Non Finnish (NFE)

AF:

0.0160

AC:

1041

AN:

64932

Other (OTH)

AF:

0.0461

AC:

AN:

2018

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

327

654

981

1308

1635

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

152

228

304

380

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0281

Hom.:

Bravo

AF:

0.0476

Asia WGS

AF:

0.0950

AC:

330

AN:

3478

EpiCase

AF:

0.0162

EpiControl

AF:

0.0172

ClinVar

Significance: Benign

Submissions summary: Uncertain:2Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Jul 29, 2019

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Uncertain:1Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Inherited Neuropathy Consortium

Significance:Uncertain significance

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Charcot-Marie-Tooth disease type 1D

Uncertain:1Benign:1

Jan 06, 2016

Inherited Neuropathy Consortium Ii, University Of Miami

Significance:Uncertain significance

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Charcot-Marie-Tooth disease

Benign:1

Molecular Genetics Laboratory, London Health Sciences Centre

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Charcot-Marie-Tooth disease, type I

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

-0.62

CADD

Benign

7.0

(source)

DANN

Benign

0.54

PhyloP100

0.045

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over