Variant 10-62812920-A-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_000399.5(EGR2):c.*287T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0631 in 337,154 control chromosomes in the GnomAD database, including 836 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.056 ( 314 hom., cov: 32)

Exomes 𝑓: 0.069 ( 522 hom. )

Consequence

EGR2
NM_000399.5 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.86

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 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=-0.62).

BP6

Variant 10-62812920-A-T is Benign according to our data. Variant chr10-62812920-A-T is described in ClinVar as [Benign]. Clinvar id is 300273.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.155 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EGR2	NM_000399.5 linkuse as main transcript	c.*287T>A		3_prime_UTR_variant	2/2	ENST00000242480.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EGR2	ENST00000242480.4 linkuse as main transcript	c.*287T>A		3_prime_UTR_variant	2/2	1	NM_000399.5	A1	P11161-1

Frequencies

GnomAD3 genomes

AF:

0.0559

AC:

8506

AN:

152186

Hom.:

312

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0145

Gnomad AMI

AF:

0.124

Gnomad AMR

AF:

0.0595

Gnomad ASJ

AF:

0.0432

Gnomad EAS

AF:

0.165

Gnomad SAS

AF:

0.0663

Gnomad FIN

AF:

0.0625

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.0701

Gnomad OTH

AF:

0.0526

GnomAD4 exome

AF:

0.0691

AC:

12767

AN:

184850

Hom.:

522

Cov.:

AF XY:

0.0685

AC XY:

6407

AN XY:

93554

show subpopulations

Gnomad4 AFR exome

AF:

0.0165

Gnomad4 AMR exome

AF:

0.0548

Gnomad4 ASJ exome

AF:

0.0414

Gnomad4 EAS exome

AF:

0.127

Gnomad4 SAS exome

AF:

0.0604

Gnomad4 FIN exome

AF:

0.0640

Gnomad4 NFE exome

AF:

0.0673

Gnomad4 OTH exome

AF:

0.0675

GnomAD4 genome

AF:

0.0559

AC:

8516

AN:

152304

Hom.:

314

Cov.:

AF XY:

0.0559

AC XY:

4165

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.0144

Gnomad4 AMR

AF:

0.0594

Gnomad4 ASJ

AF:

0.0432

Gnomad4 EAS

AF:

0.165

Gnomad4 SAS

AF:

0.0667

Gnomad4 FIN

AF:

0.0625

Gnomad4 NFE

AF:

0.0700

Gnomad4 OTH

AF:

0.0582

Alfa

AF:

0.0589

Hom.:

Bravo

AF:

0.0538

Asia WGS

AF:

0.127

AC:

440

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 16, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Charcot-Marie-Tooth disease type 1D

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Benign

0.84

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