18-36129968-T-C

Position:

• chr18-36129968-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_018255.4(ELP2):​c.35T>C​(p.Phe12Ser) 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. 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: 2.37

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31615186).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ELP2	NM_018255.4	c.35T>C	p.Phe12Ser	missense_variant	1/22	ENST00000358232.11	NP_060725.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ELP2	ENST00000358232.11	c.35T>C	p.Phe12Ser	missense_variant	1/22	1	NM_018255.4	ENSP00000350967	P1

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 11, 2024

The c.35T>C (p.F12S) alteration is located in exon 1 (coding exon 1) of the ELP2 gene. This alteration results from a T to C substitution at nucleotide position 35, causing the phenylalanine (F) at amino acid position 12 to be replaced by a serine (S). 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	Pathogenic	0.57
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.060
CADD	Uncertain	24
DANN	Benign	0.92
DEOGEN2	Benign	0.0073	T;.;.;.;.;.
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.073
FATHMM_MKL	Benign	0.29	N
LIST_S2	Uncertain	0.86	D;T;T;T;T;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.32	T;T;T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.70	N;N;N;N;N;N
MutationTaster	Benign	0.83	D;D;D;D;D;D
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-0.94	N;N;N;N;N;N
REVEL	Benign	0.22
Sift	Benign	0.70	T;T;T;T;T;T
Sift4G	Benign	0.60	T;T;T;T;T;T
Polyphen		0.12	B;B;.;.;.;B
Vest4		0.80
MutPred		0.68		Gain of disorder (P = 0.0238);Gain of disorder (P = 0.0238);Gain of disorder (P = 0.0238);Gain of disorder (P = 0.0238);Gain of disorder (P = 0.0238);Gain of disorder (P = 0.0238);
MVP		0.33
MPC		0.16
ClinPred		0.56	D
GERP RS		5.6
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.9
Varity_R		0.36
gMVP		0.61

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: rs920708444; hg19: chr18-33709931;