NM_018255.4:c.49C>G

Variant names:

• chr18-36129982-C-G
• rs773516584
• NM_018255.4:c.49C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_018255.4(ELP2):​c.49C>G​(p.Arg17Gly) 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R17W) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ELP2 NM_018255.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.981
• Publications: 0 publications found

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]

ELP2 Gene-Disease associations (from GenCC):

• intellectual disability, autosomal recessive 58

  Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018255.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELP2	NM_018255.4	MANE Select	c.49C>G	p.Arg17Gly	missense	Exon 1 of 22	NP_060725.1	Q6IA86-1
	ELP2	NM_001242875.3		c.49C>G	p.Arg17Gly	missense	Exon 1 of 23	NP_001229804.1	Q6IA86-6
	ELP2	NM_001324466.2		c.49C>G	p.Arg17Gly	missense	Exon 1 of 22	NP_001311395.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELP2	ENST00000358232.11	TSL:1 MANE Select	c.49C>G	p.Arg17Gly	missense	Exon 1 of 22	ENSP00000350967.6	Q6IA86-1
	ELP2	ENST00000423854.6	TSL:1	c.49C>G	p.Arg17Gly	missense	Exon 1 of 19	ENSP00000391202.2	Q6IA86-7
	ELP2	ENST00000542824.5	TSL:1	c.49C>G	p.Arg17Gly	missense	Exon 1 of 20	ENSP00000443800.1	Q6IA86-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.16
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Benign	0.31	N
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.083	D
MetaRNN	Uncertain	0.45	T
MetaSVM	Uncertain	-0.061	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		0.98
PrimateAI	Uncertain	0.53	T
PROVEAN	Pathogenic	-5.8	D
REVEL	Uncertain	0.43
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0050	D
Polyphen		0.99	D
Vest4		0.36
MutPred		0.65		Loss of MoRF binding (P = 0.068)
MVP		0.76
MPC		0.11
ClinPred		0.99	D
GERP RS		4.7
PromoterAI		-0.026	Neutral
Varity_R		0.76
gMVP		0.69
Mutation Taster		=58/42	polymorphism

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

Other links and lift over

dbSNP: rs773516584; hg19: chr18-33709945;