chr10-62813394-C-T

Position:

• chr10-62813394-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1 PM2

The NM_000399.5(EGR2):​c.1244G>A​(p.Arg415His) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: EGR2 NM_000399.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.17

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM1: In a zinc_finger_region C2H2-type 3 (size 22) in uniprot entity EGR2_HUMAN there are 4 pathogenic changes around while only 0 benign (100%) in NM_000399.5
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EGR2	NM_000399.5	c.1244G>A	p.Arg415His	missense_variant	2/2	ENST00000242480.4	NP_000390.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EGR2	ENST00000242480.4	c.1244G>A	p.Arg415His	missense_variant	2/2	1	NM_000399.5	ENSP00000242480.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Athena Diagnostics

Mar 31, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.95
BayesDel_addAF	Uncertain	0.013	T
BayesDel_noAF	Benign	-0.22
CADD	Pathogenic	33
DANN	Pathogenic	1.0
DEOGEN2	Pathogenic	0.84	D;.;D
Eigen	Pathogenic	0.71
Eigen_PC	Pathogenic	0.70
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.93	.;D;D
M_CAP	Benign	0.015	T
MetaRNN	Uncertain	0.59	D;D;D
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.3	M;.;M
PrimateAI	Pathogenic	0.92	D
PROVEAN	Uncertain	-4.2	D;D;D
REVEL	Uncertain	0.34
Sift	Pathogenic	0.0	D;D;D
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		1.0	D;D;D
Vest4		0.58
MutPred		0.55		Gain of methylation at K418 (P = 0.0779);.;Gain of methylation at K418 (P = 0.0779);
MVP		0.68
MPC		2.1
ClinPred		1.0	D
GERP RS		4.8
Varity_R		0.81
gMVP		0.88

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: rs1422314988; hg19: chr10-64573154; COSMIC: COSV54347801; COSMIC: COSV54347801;