chr18-36136313-C-T

Variant names:

• chr18-36136313-C-T
• rs74438152
• NM_018255.4:c.224C>T

Variant summary

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

The NM_018255.4(ELP2):​c.224C>T​(p.Ser75Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ELP2 NM_018255.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.15

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ELP2	NM_018255.4	c.224C>T	p.Ser75Phe	missense_variant	Exon 3 of 22	ENST00000358232.11	NP_060725.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ELP2	ENST00000358232.11	c.224C>T	p.Ser75Phe	missense_variant	Exon 3 of 22	1	NM_018255.4	ENSP00000350967.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.018	T
BayesDel_noAF	Benign	-0.26
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	T;.;.;.;.;.
Eigen	Benign	0.096
Eigen_PC	Benign	0.077
FATHMM_MKL	Benign	0.54	D
LIST_S2	Uncertain	0.94	D;D;D;D;D;D
M_CAP	Benign	0.062	D
MetaRNN	Uncertain	0.57	D;D;D;D;D;D
MetaSVM	Benign	-0.79	T
MutationAssessor	Uncertain	2.2	M;M;M;M;M;M
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-3.2	D;D;D;D;D;D
REVEL	Benign	0.19
Sift	Uncertain	0.017	D;D;D;D;D;D
Sift4G	Uncertain	0.027	D;D;D;D;D;D
Polyphen		0.99	D;P;.;.;.;D
Vest4		0.50
MutPred		0.66		Loss of disorder (P = 0.0036);Loss of disorder (P = 0.0036);Loss of disorder (P = 0.0036);Loss of disorder (P = 0.0036);Loss of disorder (P = 0.0036);Loss of disorder (P = 0.0036);
MVP		0.66
MPC		0.40
ClinPred		0.96	D
GERP RS		2.2
Varity_R		0.11
gMVP		0.39

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs74438152; hg19: chr18-33716276;