Variant chr10-62812919-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_000399.5(EGR2):c.*288G>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 0.00837 in 335,248 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0074 ( 7 hom., cov: 32)

Exomes 𝑓: 0.0092 ( 11 hom. )

Consequence

EGR2
NM_000399.5 3_prime_UTR

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.948

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=-0.57).

BP6

Variant 10-62812919-C-T is Benign according to our data. Variant chr10-62812919-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 300272.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00742 (1130/152326) while in subpopulation NFE AF= 0.0121 (821/68032). AF 95% confidence interval is 0.0114. There are 7 homozygotes in gnomad4. There are 515 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 7 SD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EGR2	NM_000399.5 linkuse as main transcript	c.*288G>A		3_prime_UTR_variant	2/2	ENST00000242480.4	NP_000390.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EGR2	ENST00000242480.4 linkuse as main transcript	c.*288G>A		3_prime_UTR_variant	2/2	1	NM_000399.5	ENSP00000242480	A1	P11161-1

Frequencies

GnomAD3 genomes

AF:

0.00743

AC:

1131

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00224

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00720

Gnomad ASJ

AF:

0.00806

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00186

Gnomad FIN

AF:

0.00471

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0121

Gnomad OTH

AF:

0.00813

GnomAD4 exome

AF:

0.00916

AC:

1676

AN:

182922

Hom.:

Cov.:

AF XY:

0.00936

AC XY:

867

AN XY:

92658

show subpopulations

Gnomad4 AFR exome

AF:

0.00223

Gnomad4 AMR exome

AF:

0.00567

Gnomad4 ASJ exome

AF:

0.00651

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00140

Gnomad4 FIN exome

AF:

0.00596

Gnomad4 NFE exome

AF:

0.0119

Gnomad4 OTH exome

AF:

0.00877

GnomAD4 genome

AF:

0.00742

AC:

1130

AN:

152326

Hom.:

Cov.:

AF XY:

0.00691

AC XY:

515

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.00224

Gnomad4 AMR

AF:

0.00719

Gnomad4 ASJ

AF:

0.00806

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.00471

Gnomad4 NFE

AF:

0.0121

Gnomad4 OTH

AF:

0.00804

Alfa

AF:

0.00980

Hom.:

Bravo

AF:

0.00701

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 19, 2018	- -

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

-0.57

CADD

Benign

DANN

Benign

0.85

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