5-95900755-C-T

Position:

• chr5-95900755-C-T

Variant summary

Our verdict is Benign. Variant got -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. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• 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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
ELL2	NM_012081.6	c.892G>A	p.Ala298Thr	missense_variant	7/12	ENST00000237853.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ELL2	ENST00000237853.9	c.892G>A	p.Ala298Thr	missense_variant	7/12	1	NM_012081.6	P1
ELL2	ENST00000513343.1	c.346G>A	p.Ala116Thr	missense_variant	4/5	3
ELL2	ENST00000505584.1	n.203G>A		non_coding_transcript_exon_variant	2/2	2

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

GnomAD3 exomes AF: 0.269 AC: 65519 AN: 243116 Hom.: 9346 AF XY: 0.271 AC XY: 35604 AN XY: 131294

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 SAS exome AF: 0.309

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

Gnomad4 AFR exome AF: 0.349

Gnomad4 AMR exome AF: 0.199

Gnomad4 ASJ exome AF: 0.209

Gnomad4 EAS exome AF: 0.352

Gnomad4 SAS exome AF: 0.322

Gnomad4 FIN exome AF: 0.273

Gnomad4 NFE exome AF: 0.261

Gnomad4 OTH exome AF: 0.282

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

Gnomad4 AFR AF: 0.353

Gnomad4 AMR AF: 0.235

Gnomad4 ASJ AF: 0.208

Gnomad4 EAS AF: 0.407

Gnomad4 SAS AF: 0.356

Gnomad4 FIN AF: 0.274

Gnomad4 NFE AF: 0.263

Gnomad4 OTH AF: 0.281

Alfa AF: 0.268 Hom.: 10389

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;.
MutationTaster	Benign	0.98	P;P
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

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