rs3815768

Positions:

• chr5-95900755-C-G
• chr5-95900755-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_012081.6(ELL2):​c.892G>C​(p.Ala298Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A298T) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• 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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16576192).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ELL2	NM_012081.6	c.892G>C	p.Ala298Pro	missense_variant	7/12	ENST00000237853.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ELL2	ENST00000237853.9	c.892G>C	p.Ala298Pro	missense_variant	7/12	1	NM_012081.6	P1
ELL2	ENST00000513343.1	c.346G>C	p.Ala116Pro	missense_variant	4/5	3
ELL2	ENST00000505584.1	n.203G>C		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0076	T;T
Eigen	Benign	0.049
Eigen_PC	Benign	0.14
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.85	T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.17	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.58	N;.
MutationTaster	Benign	0.94	P;P
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.59	N;N
REVEL	Benign	0.052
Sift	Benign	0.13	T;T
Sift4G	Benign	0.17	T;.
Polyphen		0.84	P;.
Vest4		0.41
MutPred		0.14		Loss of catalytic residue at A298 (P = 0.0317);.;
MVP		0.36
MPC		0.58
ClinPred		0.69	D
GERP RS		3.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.12
gMVP		0.27

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;