Genetic Variant ELL2:p.Asp312Asp (chr5-95900711-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_012081.6(ELL2):c.936C>T(p.Asp312Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.267 in 1,578,646 control chromosomes in the GnomAD database, including 58,797 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.29 ( 6543 hom., cov: 32)

Exomes 𝑓: 0.26 ( 52254 hom. )

Consequence

ELL2
NM_012081.6 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.271

Publications

33 publications found

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:

ENSG00000250362 (HGNC:):

ENSG00000250362 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP7

Synonymous conserved (PhyloP=-0.271 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.393 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ELL2	NM_012081.6 link	c.936C>T	p.Asp312Asp	synonymous_variant	Exon 7 of 12	ENST00000237853.9	NP_036213.2	O00472-1Q59FW6Q7Z656

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ELL2	ENST00000237853.9 link	c.936C>T	p.Asp312Asp	synonymous_variant	Exon 7 of 12	1	NM_012081.6	ENSP00000237853.4		O00472-1

Frequencies

GnomAD3 genomes

AF:

0.290

AC:

44043

AN:

151938

Hom.:

6531

Cov.:

show subpopulations

Gnomad AFR

AF:

0.345

Gnomad AMI

AF:

0.243

Gnomad AMR

AF:

0.235

Gnomad ASJ

AF:

0.208

Gnomad EAS

AF:

0.409

Gnomad SAS

AF:

0.355

Gnomad FIN

AF:

0.274

Gnomad MID

AF:

0.278

Gnomad NFE

AF:

0.263

Gnomad OTH

AF:

0.279

GnomAD2 exomes

AF:

0.264

AC:

62323

AN:

235726

AF XY:

0.266

show subpopulations

Gnomad AFR exome

AF:

0.343

Gnomad AMR exome

AF:

0.188

Gnomad ASJ exome

AF:

0.189

Gnomad EAS exome

AF:

0.400

Gnomad FIN exome

AF:

0.266

Gnomad NFE exome

AF:

0.251

Gnomad OTH exome

AF:

0.240

GnomAD4 exome

AF:

0.265

AC:

377761

AN:

1426590

Hom.:

52254

Cov.:

AF XY:

0.267

AC XY:

189402

AN XY:

709860

show subpopulations

African (AFR)

AF:

0.338

AC:

10855

AN:

32132

American (AMR)

AF:

0.191

AC:

7862

AN:

41130

Ashkenazi Jewish (ASJ)

AF:

0.205

AC:

5173

AN:

25196

East Asian (EAS)

AF:

0.351

AC:

13835

AN:

39400

South Asian (SAS)

AF:

0.317

AC:

25839

AN:

81608

European-Finnish (FIN)

AF:

0.271

AC:

14304

AN:

52760

Middle Eastern (MID)

AF:

0.230

AC:

1293

AN:

5628

European-Non Finnish (NFE)

AF:

0.259

AC:

282132

AN:

1089754

Other (OTH)

AF:

0.279

AC:

16468

AN:

58982

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.415

Heterozygous variant carriers

12117

24235

36352

48470

60587

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9610

19220

28830

38440

48050

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.290

AC:

44090

AN:

152056

Hom.:

6543

Cov.:

AF XY:

0.290

AC XY:

21544

AN XY:

74308

show subpopulations

African (AFR)

AF:

0.346

AC:

14327

AN:

41456

American (AMR)

AF:

0.235

AC:

3589

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.208

AC:

722

AN:

3470

East Asian (EAS)

AF:

0.408

AC:

2113

AN:

5180

South Asian (SAS)

AF:

0.356

AC:

1717

AN:

4822

European-Finnish (FIN)

AF:

0.274

AC:

2888

AN:

10554

Middle Eastern (MID)

AF:

0.272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.263

AC:

17845

AN:

67972

Other (OTH)

AF:

0.279

AC:

588

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1653

3306

4958

6611

8264

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

452

904

1356

1808

2260

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.263

Hom.:

8394

Bravo

AF:

0.289

Asia WGS

AF:

0.373

AC:

1298

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

1.5

(source)

DANN

Benign

0.74

PhyloP100

-0.27

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

Splicevardb

2.0

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over