rs224083

chr10-62814011-T-Cchr10-62814011-T-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_000399.5(EGR2):c.627A>G(p.Pro209=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0027 in 1,613,718 control chromosomes in the GnomAD database, including 107 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.015 (55 hom., cov: 32)
  • Exomes 𝑓: 0.0015 (52 hom.)
• Consequence: EGR2 NM_000399.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -4.40

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 Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 10-62814011-T-C is Benign according to our data. Variant chr10-62814011-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 415908.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-4.4 with no splicing effect.
• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0511 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EGR2	NM_000399.5	c.627A>G	p.Pro209=	synonymous_variant	2/2	ENST00000242480.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EGR2	ENST00000242480.4	c.627A>G	p.Pro209=	synonymous_variant	2/2	1	NM_000399.5	A1

Frequencies

GnomAD3 genomes AF: 0.0147 AC: 2225 AN: 151710 Hom.: 55 Cov.: 32

Gnomad AFR AF: 0.0516

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00420

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.0130

GnomAD4 exome AF: 0.00145 AC: 2122 AN: 1461890 Hom.: 52 Cov.: 31 AF XY: 0.00127 AC XY: 927 AN XY: 727244

Gnomad4 AFR exome AF: 0.0531

Gnomad4 AMR exome AF: 0.00284

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000104

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000126

Gnomad4 OTH exome AF: 0.00310

GnomAD4 genome AF: 0.0147 AC: 2229 AN: 151828 Hom.: 55 Cov.: 32 AF XY: 0.0139 AC XY: 1031 AN XY: 74206

Gnomad4 AFR AF: 0.0515

Gnomad4 AMR AF: 0.00419

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000103

Gnomad4 OTH AF: 0.0128

Alfa AF: 0.00939 Hom.: 18

Bravo AF: 0.0168

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Athena Diagnostics

Sep 15, 2020

- -

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

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	1.4

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs224083; hg19: chr10-64573771;