rs17085249

chr5-95900711-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_012081.6(ELL2):c.936C>T(p.Asp312=) 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.271

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 -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/exons	MANE	UniProt
ELL2	NM_012081.6	c.936C>T	p.Asp312=	synonymous_variant	7/12	ENST00000237853.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ELL2	ENST00000237853.9	c.936C>T	p.Asp312=	synonymous_variant	7/12	1	NM_012081.6	P1
ELL2	ENST00000513343.1	c.390C>T	p.Asp130=	synonymous_variant	4/5	3
ELL2	ENST00000505584.1	n.247C>T		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes AF: 0.290 AC: 44043 AN: 151938 Hom.: 6531 Cov.: 32

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

GnomAD3 exomes AF: 0.264 AC: 62323 AN: 235726 Hom.: 8727 AF XY: 0.266 AC XY: 33831 AN XY: 127250

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 SAS exome AF: 0.301

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.: 30 AF XY: 0.267 AC XY: 189402 AN XY: 709860

Gnomad4 AFR exome AF: 0.338

Gnomad4 AMR exome AF: 0.191

Gnomad4 ASJ exome AF: 0.205

Gnomad4 EAS exome AF: 0.351

Gnomad4 SAS exome AF: 0.317

Gnomad4 FIN exome AF: 0.271

Gnomad4 NFE exome AF: 0.259

Gnomad4 OTH exome AF: 0.279

GnomAD4 genome AF: 0.290 AC: 44090 AN: 152056 Hom.: 6543 Cov.: 32 AF XY: 0.290 AC XY: 21544 AN XY: 74308

Gnomad4 AFR AF: 0.346

Gnomad4 AMR AF: 0.235

Gnomad4 ASJ AF: 0.208

Gnomad4 EAS AF: 0.408

Gnomad4 SAS AF: 0.356

Gnomad4 FIN AF: 0.274

Gnomad4 NFE AF: 0.263

Gnomad4 OTH AF: 0.279

Alfa AF: 0.260 Hom.: 6225

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
Dann	Benign	0.74
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
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

LitVar

Other links and lift over

dbSNP: rs17085249; hg19: chr5-95236415; COSMIC: COSV52982568; COSMIC: COSV52982568;