rs2297489

chr10-62815600-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000399.5(EGR2):c.169+261G>C variant causes a intron 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 NM_000399.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.764

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 id 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/exons	MANE	UniProt
EGR2	NM_000399.5	c.169+261G>C		intron_variant		ENST00000242480.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EGR2	ENST00000242480.4	c.169+261G>C		intron_variant		1	NM_000399.5	A1
	ENST00000493899.2	n.650+261G>C		intron_variant, non_coding_transcript_variant		5

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

Gnomad4 AFR AF: 0.0153

Gnomad4 AMR AF: 0.0560

Gnomad4 ASJ AF: 0.0467

Gnomad4 EAS AF: 0.200

Gnomad4 SAS AF: 0.0853

Gnomad4 FIN AF: 0.0625

Gnomad4 NFE AF: 0.0701

Gnomad4 OTH AF: 0.0619

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

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 16, 2018

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

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

Other links and lift over

dbSNP: rs2297489; hg19: chr10-64575360;