5-95900755-C-T

Variant names:

• chr5-95900755-C-T
• rs3815768
• NM_012081.6:c.892G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012081.6(ELL2):​c.892G>A​(p.Ala298Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.27 in 1,593,504 control chromosomes in the GnomAD database, including 60,468 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict 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 (6655 hom., cov: 33)
  • Exomes 𝑓: 0.27 (53813 hom.)
• Consequence: ELL2 NM_012081.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.17
• Publications: 44 publications found

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]

ENSG00000250362 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0034206808).
• 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	c.892G>A	p.Ala298Thr	missense_variant	Exon 7 of 12	ENST00000237853.9	NP_036213.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ELL2	ENST00000237853.9	c.892G>A	p.Ala298Thr	missense_variant	Exon 7 of 12	1	NM_012081.6	ENSP00000237853.4

Frequencies

GnomAD3 genomes AF: 0.292 AC: 44380 AN: 152040 Hom.: 6642 Cov.: 33

Gnomad AFR AF: 0.352

Gnomad AMI AF: 0.243

Gnomad AMR AF: 0.235

Gnomad ASJ AF: 0.208

Gnomad EAS AF: 0.408

Gnomad SAS AF: 0.355

Gnomad FIN AF: 0.274

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.263

Gnomad OTH AF: 0.280

GnomAD2 exomes AF: 0.269 AC: 65519 AN: 243116 AF XY: 0.271

Gnomad AFR exome AF: 0.353

Gnomad AMR exome AF: 0.197

Gnomad ASJ exome AF: 0.201

Gnomad EAS exome AF: 0.405

Gnomad FIN exome AF: 0.269

Gnomad NFE exome AF: 0.254

Gnomad OTH exome AF: 0.246

GnomAD4 exome AF: 0.268 AC: 385885 AN: 1441346 Hom.: 53813 Cov.: 32 AF XY: 0.270 AC XY: 193427 AN XY: 717326

African (AFR) AF: 0.349 AC: 11407 AN: 32720

American (AMR) AF: 0.199 AC: 8601 AN: 43140

Ashkenazi Jewish (ASJ) AF: 0.209 AC: 5369 AN: 25672

East Asian (EAS) AF: 0.352 AC: 13925 AN: 39550

South Asian (SAS) AF: 0.322 AC: 27038 AN: 83952

European-Finnish (FIN) AF: 0.273 AC: 14457 AN: 53000

Middle Eastern (MID) AF: 0.232 AC: 1318 AN: 5690

European-Non Finnish (NFE) AF: 0.261 AC: 286981 AN: 1098098

Other (OTH) AF: 0.282 AC: 16789 AN: 59524

GnomAD4 genome AF: 0.292 AC: 44429 AN: 152158 Hom.: 6655 Cov.: 33 AF XY: 0.292 AC XY: 21719 AN XY: 74386

African (AFR) AF: 0.353 AC: 14633 AN: 41504

American (AMR) AF: 0.235 AC: 3600 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.208 AC: 722 AN: 3472

East Asian (EAS) AF: 0.407 AC: 2113 AN: 5186

South Asian (SAS) AF: 0.356 AC: 1718 AN: 4830

European-Finnish (FIN) AF: 0.274 AC: 2893 AN: 10572

Middle Eastern (MID) AF: 0.272 AC: 80 AN: 294

European-Non Finnish (NFE) AF: 0.263 AC: 17856 AN: 67980

Other (OTH) AF: 0.281 AC: 592 AN: 2108

Alfa AF: 0.271 Hom.: 15688

Bravo AF: 0.292

TwinsUK AF: 0.253 AC: 937

ALSPAC AF: 0.265 AC: 1021

ESP6500AA AF: 0.349 AC: 1538

ESP6500EA AF: 0.261 AC: 2248

ExAC AF: 0.281 AC: 34143

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
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.68	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	17
DANN	Benign	0.82
DEOGEN2	Benign	0.0036	T;T
Eigen	Benign	-0.70
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.78	T;T
MetaRNN	Benign	0.0034	T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	-1.0	N;.
PhyloP100		1.2
PrimateAI	Benign	0.30	T
PROVEAN	Benign	1.2	N;N
REVEL	Benign	0.095
Sift	Benign	0.94	T;T
Sift4G	Benign	0.88	T;.
Polyphen		0.0	B;.
Vest4		0.035
MPC		0.43
ClinPred		0.014	T
GERP RS		3.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.042
gMVP		0.20
Mutation Taster		=95/5	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3815768; hg19: chr5-95236459; COSMIC: COSV52982576; COSMIC: COSV52982576;