Variant 5-95943025-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_012081.6(ELL2):c.172A>G(p.Ile58Val) variant causes a missense change. The variant allele was found at a frequency of 0.00603 in 1,601,978 control chromosomes in the GnomAD database, including 41 homozygotes. 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 Likely benign (★★).

Frequency

Genomes: 𝑓 0.0042 ( 5 hom., cov: 32)

Exomes 𝑓: 0.0062 ( 36 hom. )

Consequence

ELL2
NM_012081.6 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.64

Variant links:

Genes affected

ELL2 (HGNC:17064): (elongation factor for RNA polymerase II 2) Involved in snRNA transcription by RNA polymerase II. Located in nucleoplasm. Part of transcription elongation factor complex. [provided by Alliance of Genome Resources, Apr 2022]

ELL2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010061741).

BP6

Variant 5-95943025-T-C is Benign according to our data. Variant chr5-95943025-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 773461.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ELL2	NM_012081.6 linkuse as main transcript	c.172A>G	p.Ile58Val	missense_variant	2/12	ENST00000237853.9	NP_036213.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ELL2	ENST00000237853.9 linkuse as main transcript	c.172A>G	p.Ile58Val	missense_variant	2/12	1	NM_012081.6	ENSP00000237853	P1	O00472-1

Frequencies

GnomAD3 genomes

AF:

0.00419

AC:

638

AN:

152096

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00167

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00524

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00703

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00302

AC:

735

AN:

243470

Hom.:

AF XY:

0.00300

AC XY:

396

AN XY:

131864

show subpopulations

Gnomad AFR exome

AF:

0.00127

Gnomad AMR exome

AF:

0.00166

Gnomad ASJ exome

AF:

0.000100

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000581

Gnomad FIN exome

AF:

0.000465

Gnomad NFE exome

AF:

0.00552

Gnomad OTH exome

AF:

0.00327

GnomAD4 exome

AF:

0.00622

AC:

9018

AN:

1449766

Hom.:

Cov.:

AF XY:

0.00596

AC XY:

4298

AN XY:

721188

show subpopulations

Gnomad4 AFR exome

AF:

0.000881

Gnomad4 AMR exome

AF:

0.00209

Gnomad4 ASJ exome

AF:

0.0000771

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000605

Gnomad4 FIN exome

AF:

0.000471

Gnomad4 NFE exome

AF:

0.00769

Gnomad4 OTH exome

AF:

0.00533

GnomAD4 genome

AF:

0.00418

AC:

637

AN:

152212

Hom.:

Cov.:

AF XY:

0.00382

AC XY:

284

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.00166

Gnomad4 AMR

AF:

0.00523

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.00702

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00580

Hom.:

Bravo

AF:

0.00490

TwinsUK

AF:

0.00755

AC:

ALSPAC

AF:

0.00960

AC:

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00721

AC:

ExAC

AF:

0.00303

AC:

368

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 27, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.030

T;T

Eigen

Benign

0.063

Eigen_PC

Benign

0.16

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.79

T;T

M_CAP

Benign

0.013

MetaRNN

Benign

0.010

T;T

MetaSVM

Benign

-0.85

MutationAssessor

Uncertain

2.3

M;.

MutationTaster

Benign

0.99

D;N

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-0.75

N;N

REVEL

Benign

0.15

Sift

Uncertain

0.0090

D;T

Sift4G

Uncertain

0.019

D;.

Polyphen

0.0010

B;.

Vest4

0.49

MVP

0.38

MPC

0.38

ClinPred

0.022

GERP RS

4.7

Varity_R

0.16

gMVP

0.23

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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