rs61865882

Variant names:

• chr10-62812333-T-C
• rs61865882
• ENST00000439032.6:n.*2320A>G

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The ENST00000439032.6(EGR2):​n.*2320A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0559 in 152,886 control chromosomes in the GnomAD database, including 313 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.056 (312 hom., cov: 33)
  • Exomes 𝑓: 0.077 (1 hom.)
• Consequence: EGR2 ENST00000439032.6 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.83
• Publications: 11 publications found

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 Gene-Disease associations (from GenCC):

• Charcot-Marie-Tooth disease type 4E

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae), G2P
• Charcot-Marie-Tooth disease

  Inheritance: SD Classification: DEFINITIVE Submitted by: ClinGen
• Charcot-Marie-Tooth disease type 1D

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• Charcot-Marie-Tooth disease type 3

  Inheritance: SD, AD Classification: MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet

ACMG classification

Our verdict: Benign. The variant received -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP6: Variant 10-62812333-T-C is Benign according to our data. Variant chr10-62812333-T-C is described in ClinVar as Benign. ClinVar VariationId is 300266.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.153 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000439032.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EGR2	NM_000399.5	MANE Select	c.*874A>G		3_prime_UTR	Exon 2 of 2	NP_000390.2
	EGR2	NM_001410931.1		c.*874A>G		3_prime_UTR	Exon 3 of 3	NP_001397860.1
	EGR2	NM_001136177.3		c.*874A>G		3_prime_UTR	Exon 3 of 3	NP_001129649.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EGR2	ENST00000439032.6	TSL:1	n.*2320A>G		non_coding_transcript_exon	Exon 2 of 2	ENSP00000509775.1
	EGR2	ENST00000242480.4	TSL:1 MANE Select	c.*874A>G		3_prime_UTR	Exon 2 of 2	ENSP00000242480.3
	EGR2	ENST00000439032.6	TSL:1	n.*2320A>G		3_prime_UTR	Exon 2 of 2	ENSP00000509775.1

Frequencies

GnomAD3 genomes AF: 0.0558 AC: 8485 AN: 152196 Hom.: 310 Cov.: 33

Gnomad AFR AF: 0.0145

Gnomad AMI AF: 0.124

Gnomad AMR AF: 0.0595

Gnomad ASJ AF: 0.0418

Gnomad EAS AF: 0.162

Gnomad SAS AF: 0.0631

Gnomad FIN AF: 0.0626

Gnomad MID AF: 0.0573

Gnomad NFE AF: 0.0702

Gnomad OTH AF: 0.0546

GnomAD4 exome AF: 0.0769 AC: 44 AN: 572 Hom.: 1 Cov.: 0 AF XY: 0.0749 AC XY: 25 AN XY: 334

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.0870 AC: 12 AN: 138

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.0724 AC: 31 AN: 428

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AF: 0.250 AC: 1 AN: 4

GnomAD4 genome AF: 0.0558 AC: 8495 AN: 152314 Hom.: 312 Cov.: 33 AF XY: 0.0558 AC XY: 4155 AN XY: 74480

African (AFR) AF: 0.0144 AC: 600 AN: 41562

American (AMR) AF: 0.0594 AC: 909 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0418 AC: 145 AN: 3466

East Asian (EAS) AF: 0.162 AC: 839 AN: 5190

South Asian (SAS) AF: 0.0636 AC: 307 AN: 4828

European-Finnish (FIN) AF: 0.0626 AC: 665 AN: 10620

Middle Eastern (MID) AF: 0.0651 AC: 19 AN: 292

European-Non Finnish (NFE) AF: 0.0701 AC: 4771 AN: 68028

Other (OTH) AF: 0.0602 AC: 127 AN: 2110

Alfa AF: 0.0621 Hom.: 67

Bravo AF: 0.0537

Asia WGS AF: 0.124 AC: 430 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Charcot-Marie-Tooth disease type 1D (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	14
DANN	Benign	0.88
PhyloP100		1.8
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs61865882; hg19: chr10-64572093;