Variant rs747574524 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PP5_ModerateBP4BS2

The NM_001331036.3(ELF2):c.10G>A(p.Ala4Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000226 in 1,461,666 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

ELF2
NM_001331036.3 missense

Scores

Clinical Significance

Likely pathogenic criteria provided, single submitter P:1U:1

Conservation

PhyloP100: 4.58

Variant links:

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]

ELF2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PP5

Variant 4-139137692-C-T is Pathogenic according to our data. Variant chr4-139137692-C-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 431175.Status of the report is criteria_provided_single_submitter, 1 stars.

BP4

Computational evidence support a benign effect (MetaRNN=0.28851974). . Strength limited to SUPPORTING due to the PP5.

BS2

High AC in GnomAdExome4 at 33 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ELF2	NM_001331036.3 linkuse as main transcript	c.10G>A	p.Ala4Thr	missense_variant	3/10	ENST00000686138.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ELF2	ENST00000686138.1 linkuse as main transcript	c.10G>A	p.Ala4Thr	missense_variant	3/10		NM_001331036.3	P1	Q15723-5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000226

AC:

AN:

1461666

Hom.:

Cov.:

AF XY:

0.0000220

AC XY:

AN XY:

727136

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000297

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Cerebellar ataxia with neuropathy and bilateral vestibular areflexia syndrome

Pathogenic:1

Likely pathogenic, criteria provided, single submitter

in vitro;research

Otology & Neurotology- Genomics of vestibular disorders (CTS-495), Jose Antonio López Escámez, Centro Pfizer - Universidad de Granada - Junta de Andalucía de Genómica e Investigación Oncológica (GENYO)

Aug 03, 2017

Regulates the expression of ATXN2 and ELOVL5 genes, two Ataxia genes. -

not provided

Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

OMIM

May 03, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.055

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.029

.;T

Eigen

Uncertain

0.55

Eigen_PC

Uncertain

0.57

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.92

D;D

M_CAP

Benign

0.0092

MetaRNN

Benign

0.29

T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.7

L;L

MutationTaster

Benign

0.81

D;D;D

PROVEAN

Benign

-0.44

N;N

REVEL

Benign

0.12

Sift

Benign

0.066

T;T

Sift4G

Benign

0.16

T;T

Polyphen

1.0

D;.

Vest4

0.33

MutPred

0.20

Gain of relative solvent accessibility (P = 0.09);Gain of relative solvent accessibility (P = 0.09);

MVP

0.38

MPC

0.33

ClinPred

0.74

GERP RS

5.2

Varity_R

0.12

gMVP

0.32

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over