NM_012081.6:c.936C>T

Variant names:

• chr5-95900711-G-A
• rs17085249
• NM_012081.6:c.936C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.271
• Publications: 33 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 -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012081.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELL2	NM_012081.6	MANE Select	c.936C>T	p.Asp312Asp	synonymous	Exon 7 of 12	NP_036213.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELL2	ENST00000237853.9	TSL:1 MANE Select	c.936C>T	p.Asp312Asp	synonymous	Exon 7 of 12	ENSP00000237853.4
	ELL2	ENST00000513343.1	TSL:3	c.390C>T	p.Asp130Asp	synonymous	Exon 4 of 5	ENSP00000423915.1
	ELL2	ENST00000505584.1	TSL:2	n.247C>T		non_coding_transcript_exon	Exon 2 of 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

GnomAD2 exomes AF: 0.264 AC: 62323 AN: 235726 AF XY: 0.266

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

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

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

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: 80 AN: 294

European-Non Finnish (NFE) AF: 0.263 AC: 17845 AN: 67972

Other (OTH) AF: 0.279 AC: 588 AN: 2108

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.5
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)

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

Other links and lift over

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