rs10995315

Positions:

• chr10-62814811-G-A

Variant summary

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

The NM_000399.5(EGR2):​c.170-343C>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 152,252 control chromosomes in the GnomAD database, including 360 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 (360 hom., cov: 32)
• Consequence: EGR2 NM_000399.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.232

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=-0.54).
• 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.170-343C>T		intron_variant		ENST00000242480.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EGR2	ENST00000242480.4	c.170-343C>T		intron_variant		1	NM_000399.5	A1
	ENST00000493899.2	n.651-343C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0576 AC: 8767 AN: 152134 Hom.: 358 Cov.: 32

Gnomad AFR AF: 0.0153

Gnomad AMI AF: 0.124

Gnomad AMR AF: 0.0561

Gnomad ASJ AF: 0.0467

Gnomad EAS AF: 0.200

Gnomad SAS AF: 0.0845

Gnomad FIN AF: 0.0625

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0700

Gnomad OTH AF: 0.0554

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0576 AC: 8777 AN: 152252 Hom.: 360 Cov.: 32 AF XY: 0.0578 AC XY: 4299 AN XY: 74438

Gnomad4 AFR AF: 0.0152

Gnomad4 AMR AF: 0.0560

Gnomad4 ASJ AF: 0.0467

Gnomad4 EAS AF: 0.200

Gnomad4 SAS AF: 0.0848

Gnomad4 FIN AF: 0.0625

Gnomad4 NFE AF: 0.0699

Gnomad4 OTH AF: 0.0610

Alfa AF: 0.0579 Hom.: 50

Bravo AF: 0.0547

Asia WGS AF: 0.140 AC: 487 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	10
DANN	Benign	0.66

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: rs10995315; hg19: chr10-64574571;