rs2297488

chr10-62815485-G-Achr10-62815485-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000399.5(EGR2):c.169+376C>T variant causes a intron 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 NM_000399.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.33

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 -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/exons	MANE	UniProt
EGR2	NM_000399.5	c.169+376C>T		intron_variant		ENST00000242480.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EGR2	ENST00000242480.4	c.169+376C>T		intron_variant		1	NM_000399.5	A1
	ENST00000493899.2	n.650+376C>T		intron_variant, non_coding_transcript_variant		5

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

Gnomad4 AFR AF: 0.0153

Gnomad4 AMR AF: 0.0559

Gnomad4 ASJ AF: 0.0464

Gnomad4 EAS AF: 0.200

Gnomad4 SAS AF: 0.0840

Gnomad4 FIN AF: 0.0626

Gnomad4 NFE AF: 0.0699

Gnomad4 OTH AF: 0.0606

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs2297488; hg19: chr10-64575245;