18-36129943-C-G

Position:

• chr18-36129943-C-G

Variant summary

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

The NM_018255.4(ELP2):​c.10C>G​(p.Pro4Ala) 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. 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: -0.394

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=0.09151226).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ELP2	NM_018255.4	c.10C>G	p.Pro4Ala	missense_variant	1/22	ENST00000358232.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ELP2	ENST00000358232.11	c.10C>G	p.Pro4Ala	missense_variant	1/22	1	NM_018255.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 17, 2023

The c.10C>G (p.P4A) alteration is located in exon 1 (coding exon 1) of the ELP2 gene. This alteration results from a C to G substitution at nucleotide position 10, causing the proline (P) at amino acid position 4 to be replaced by an alanine (A). 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	0.057
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	14
DANN	Benign	0.96
DEOGEN2	Benign	0.015	T;.;.;.;.;.
Eigen	Benign	-0.89
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.019	N
LIST_S2	Uncertain	0.89	D;D;D;D;D;D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.092	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.0	M;M;M;M;M;M
MutationTaster	Benign	1.0	N;N;N;N;N;N
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.9	N;N;N;N;N;N
REVEL	Benign	0.030
Sift	Benign	0.068	T;T;T;D;T;T
Sift4G	Uncertain	0.031	D;D;D;D;D;D
Polyphen		0.039	B;B;.;.;.;B
Vest4		0.30
MutPred		0.40		Loss of catalytic residue at P4 (P = 0.1278);Loss of catalytic residue at P4 (P = 0.1278);Loss of catalytic residue at P4 (P = 0.1278);Loss of catalytic residue at P4 (P = 0.1278);Loss of catalytic residue at P4 (P = 0.1278);Loss of catalytic residue at P4 (P = 0.1278);
MVP		0.44
MPC		0.085
ClinPred		0.19	T
GERP RS		1.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.033
gMVP		0.44

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: rs770664170; hg19: chr18-33709906;