4-139060333-G-A

Variant summary

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

The NM_001331036.3(ELF2):c.1148C>T(p.Ala383Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ELF2 NM_001331036.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.67

Genes affected

ELF2 (HGNC:3317): (E74 like ETS transcription factor 2) Enables DNA-binding transcription factor activity, RNA polymerase II-specific and sequence-specific double-stranded DNA binding activity. Involved in negative regulation of transcription, DNA-templated; positive regulation of transcription, DNA-templated; and regulation of transcription by RNA polymerase II. Located in cytosol and nuclear body. [provided by Alliance of Genome Resources, Apr 2022]

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=0.13987836).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ELF2	NM_001331036.3	c.1148C>T	p.Ala383Val	missense_variant	9/10	ENST00000686138.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ELF2	ENST00000686138.1	c.1148C>T	p.Ala383Val	missense_variant	9/10		NM_001331036.3	P1

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

Ambry Genetics

Jun 21, 2022

The c.1112C>T (p.A371V) alteration is located in exon 8 (coding exon 7) of the ELF2 gene. This alteration results from a C to T substitution at nucleotide position 1112, causing the alanine (A) at amino acid position 371 to be replaced by a valine (V). 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	Benign	0.083
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
Cadd	Benign	22
Dann	Uncertain	0.99
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.096
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.97	D;D;D;D;D
M_CAP	Benign	0.0085	T
MetaRNN	Benign	0.14	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	0.82	N;N;N;N;N;N
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.63	N;N;N;N;N
REVEL	Benign	0.045
Sift	Benign	0.14	T;T;T;T;T
Sift4G	Benign	0.30	T;T;T;T;T
Polyphen		0.034	B;.;.;B;.
Vest4		0.10
MutPred		0.34		.;.;.;Gain of sheet (P = 0.0221);.;
MVP		0.068
MPC		0.39
ClinPred		0.49	T
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.096
gMVP		0.35

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: rs74853835; hg19: chr4-139981487;