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. Variant got 4 ACMG points: 4P and 0B. PM2 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 (★).

• 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

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_000399.5.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EGR2	NM_000399.5	c.919_927delGCCGCCGCC	p.Ala307_Ala309del	conservative_inframe_deletion	Exon 2 of 2	ENST00000242480.4	NP_000390.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EGR2	ENST00000242480.4	c.919_927delGCCGCCGCC	p.Ala307_Ala309del	conservative_inframe_deletion	Exon 2 of 2	1	NM_000399.5	ENSP00000242480.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000246 AC: 6 AN: 243670 Hom.: 0 AF XY: 0.0000376 AC XY: 5 AN XY: 133136

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 SAS exome AF: 0.0000328

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.000192

Gnomad4 NFE exome AF: 0.0000117

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000364 Hom.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Charcot-Marie-Tooth disease, type I Uncertain:1

Sep 14, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant, c.919_927del, results in the deletion of 3 amino acid(s) of the EGR2 protein (p.Ala307_Ala309del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs758019499, gnomAD 0.02%). This variant has been observed in individual(s) with clinical features of EGR2-related conditions (internal data). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs753747037; hg19: chr10-64573470;