10-62815939-G-T

Position:

• chr10-62815939-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000399.5(EGR2):​c.91C>A​(p.Leu31Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L31F) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: EGR2 NM_000399.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.13

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]

(HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08938587).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EGR2	NM_000399.5	c.91C>A	p.Leu31Ile	missense_variant	1/2	ENST00000242480.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EGR2	ENST00000242480.4	c.91C>A	p.Leu31Ile	missense_variant	1/2	1	NM_000399.5	A1
	ENST00000493899.2	n.572C>A		non_coding_transcript_exon_variant	7/8	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	21
DANN	Benign	0.92
DEOGEN2	Benign	0.34	T;T;T
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.084
FATHMM_MKL	Benign	0.00065	N
M_CAP	Benign	0.0027	T
MetaRNN	Benign	0.089	T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	-0.30	N;N;.
MutationTaster	Benign	1.0	D;N;N
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-0.64	N;N;.
REVEL	Benign	0.038
Sift	Benign	0.37	T;T;.
Sift4G	Benign	0.56	T;T;.
Polyphen		0.012	B;B;.
Vest4		0.17
MutPred		0.30		Gain of sheet (P = 0.0221);Gain of sheet (P = 0.0221);Gain of sheet (P = 0.0221);
MVP		0.25
MPC		0.95
ClinPred		0.49	T
GERP RS		4.2
Varity_R		0.080
gMVP		0.10

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: rs535186925; hg19: chr10-64575699;