5-95898678-G-A

Position:

• chr5-95898678-G-A

Variant summary

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

The NM_012081.6(ELL2):​c.1087C>T​(p.Leu363Phe) 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.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ELL2 NM_012081.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.46

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=0.1712299).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ELL2	NM_012081.6	c.1087C>T	p.Leu363Phe	missense_variant	8/12	ENST00000237853.9	NP_036213.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ELL2	ENST00000237853.9	c.1087C>T	p.Leu363Phe	missense_variant	8/12	1	NM_012081.6	ENSP00000237853.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1460772 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 726558

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 14, 2024

The c.1087C>T (p.L363F) alteration is located in exon 8 (coding exon 8) of the ELL2 gene. This alteration results from a C to T substitution at nucleotide position 1087, causing the leucine (L) at amino acid position 363 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.013	T
Eigen	Benign	0.022
Eigen_PC	Benign	0.075
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.0057	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	2.0	M
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.63	N
REVEL	Benign	0.062
Sift	Benign	0.69	T
Sift4G	Benign	0.64	T
Polyphen		0.94	P
Vest4		0.12
MutPred		0.19		Loss of helix (P = 0.028);
MVP		0.39
MPC		1.2
ClinPred		0.82	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.099
gMVP		0.085

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: rs1748985999; hg19: chr5-95234382;