rs753747037

Variant names:

• chr10-62813710-AGGCGGCGGC-A
• rs753747037
• NM_000399.5:c.919_927delGCCGCCGCC

Your query was ambiguous. Multiple possible variants found:

• chr10-62813710-AGGCGGCGGC-A
• chr10-62813710-AGGCGGCGGC-AGGC
• chr10-62813710-AGGCGGCGGC-AGGCGGC
• chr10-62813710-AGGCGGCGGC-AGGCGGCGGCGGC
• chr10-62813710-AGGCGGCGGC-AGGCGGCGGCGGCGGC
• chr10-62813710-AGGCGGCGGC-AGGCGGCGGCGGCGGCGGC

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM4

The NM_000399.5(EGR2):​c.919_927delGCCGCCGCC​(p.Ala307_Ala309del) variant causes a conservative inframe deletion change. The variant allele was found at a frequency of 0.0000171 in 1,459,812 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. A307A) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000017 (0 hom.)
• Consequence: EGR2 NM_000399.5 conservative_inframe_deletion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.18
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_000399.5.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000399.5. 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.919_927delGCCGCCGCC	p.Ala307_Ala309del	conservative_inframe_deletion	Exon 2 of 2	NP_000390.2
	EGR2	NM_001410931.1		c.958_966delGCCGCCGCC	p.Ala320_Ala322del	conservative_inframe_deletion	Exon 3 of 3	NP_001397860.1
	EGR2	NM_001136177.3		c.919_927delGCCGCCGCC	p.Ala307_Ala309del	conservative_inframe_deletion	Exon 3 of 3	NP_001129649.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EGR2	ENST00000242480.4	TSL:1 MANE Select	c.919_927delGCCGCCGCC	p.Ala307_Ala309del	conservative_inframe_deletion	Exon 2 of 2	ENSP00000242480.3
	EGR2	ENST00000439032.6	TSL:1	n.*934_*942delGCCGCCGCC		non_coding_transcript_exon	Exon 2 of 2	ENSP00000509775.1
	EGR2	ENST00000439032.6	TSL:1	n.*934_*942delGCCGCCGCC		3_prime_UTR	Exon 2 of 2	ENSP00000509775.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000246 AC: 6 AN: 243670 AF XY: 0.0000376

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000198

Gnomad NFE exome AF: 0.00000908

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000171 AC: 25 AN: 1459812 Hom.: 0 AF XY: 0.0000234 AC XY: 17 AN XY: 726102

African (AFR) AF: 0.00 AC: 0 AN: 33472

American (AMR) AF: 0.00 AC: 0 AN: 44694

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26104

East Asian (EAS) AF: 0.00 AC: 0 AN: 39682

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86238

European-Finnish (FIN) AF: 0.000192 AC: 10 AN: 52136

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5752

European-Non Finnish (NFE) AF: 0.0000117 AC: 13 AN: 1111448

Other (OTH) AF: 0.00 AC: 0 AN: 60286

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000364 Hom.: 0

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Charcot-Marie-Tooth disease, type I (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		6.2
Mutation Taster		=158/42	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs753747037; hg19: chr10-64573470;