chr2-73291489-A-T

Position:

• chr2-73291489-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001965.4(EGR4):​c.1429T>A​(p.Tyr477Asn) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: EGR4 NM_001965.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.53

Genes affected

EGR4 (HGNC:3241): (early growth response 4) Enables DNA-binding transcription activator activity, RNA polymerase II-specific and sequence-specific double-stranded DNA binding activity. Involved in positive regulation of transcription by RNA polymerase II. Predicted to be located in nucleoplasm. Predicted to be part of chromatin. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32736915).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EGR4	NM_001965.4	c.1429T>A	p.Tyr477Asn	missense_variant	2/2	ENST00000436467.4
EGR4	XM_047443603.1	c.1426T>A	p.Tyr476Asn	missense_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EGR4	ENST00000436467.4	c.1429T>A	p.Tyr477Asn	missense_variant	2/2	1	NM_001965.4	P2
EGR4	ENST00000545030.1	c.1738T>A	p.Tyr580Asn	missense_variant	2/2	1		A2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

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

Ambry Genetics

Dec 30, 2023

The c.1738T>A (p.Y580N) alteration is located in exon 2 (coding exon 2) of the EGR4 gene. This alteration results from a T to A substitution at nucleotide position 1738, causing the tyrosine (Y) at amino acid position 580 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.91
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Pathogenic	29
DANN	Uncertain	0.99
DEOGEN2	Benign	0.15	.;T
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.88	D;D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.33	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.93	.;L
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	0.43	N;N
REVEL	Benign	0.17
Sift	Benign	0.036	D;D
Sift4G	Uncertain	0.0050	D;D
Vest4		0.48
MVP		0.69
MPC		1.1
ClinPred		0.81	D
GERP RS		4.5
Varity_R		0.21
gMVP		0.69

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-73518617;