chr18-36130016-C-T

Variant names:

• chr18-36130016-C-T
• NM_018255.4:c.83C>T

Variant summary

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

The NM_018255.4(ELP2):​c.83C>T​(p.Pro28Leu) 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. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ELP2 NM_018255.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.490

Genes affected

ELP2 (HGNC:18248): (elongator acetyltransferase complex subunit 2) The protein encoded by this gene is a core subunit of the elongator complex, a histone acetyltransferase complex that associates with RNA polymerase II. In addition to histone acetylation, the encoded protein effects transcriptional elongation and may help remodel chromatin. [provided by RefSeq, May 2016]

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=0.19526273).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ELP2	NM_018255.4	c.83C>T	p.Pro28Leu	missense_variant	Exon 1 of 22	ENST00000358232.11	NP_060725.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ELP2	ENST00000358232.11	c.83C>T	p.Pro28Leu	missense_variant	Exon 1 of 22	1	NM_018255.4	ENSP00000350967.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Feb 27, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.83C>T (p.P28L) alteration is located in exon 1 (coding exon 1) of the ELP2 gene. This alteration results from a C to T substitution at nucleotide position 83, causing the proline (P) at amino acid position 28 to be replaced by a leucine (L). 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	0.098
BayesDel_addAF	Benign	0.0049	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.095	T;.;.;.;.;.
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.20
FATHMM_MKL	Benign	0.035	N
LIST_S2	Uncertain	0.91	D;D;D;D;D;D
M_CAP	Benign	0.047	D
MetaRNN	Benign	0.20	T;T;T;T;T;T
MetaSVM	Benign	-0.58	T
MutationAssessor	Uncertain	2.3	M;M;M;M;M;M
PrimateAI	Benign	0.36	T
PROVEAN	Uncertain	-4.1	D;D;D;D;D;D
REVEL	Benign	0.12
Sift	Benign	0.066	T;T;D;T;D;D
Sift4G	Benign	0.24	T;T;T;T;T;T
Polyphen		0.078	B;B;.;.;.;B
Vest4		0.23
MutPred		0.63		Gain of MoRF binding (P = 0.0523);Gain of MoRF binding (P = 0.0523);Gain of MoRF binding (P = 0.0523);Gain of MoRF binding (P = 0.0523);Gain of MoRF binding (P = 0.0523);Gain of MoRF binding (P = 0.0523);
MVP		0.71
MPC		0.096
ClinPred		0.98	D
GERP RS		3.7
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.3
Varity_R		0.13
gMVP		0.41

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr18-33709979; COSMIC: COSV52368663; COSMIC: COSV52368663;