NM_018255.4:c.83C>T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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. 13/22 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
• 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: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19526273).

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.83C>T	p.Pro28Leu	missense	Exon 1 of 22	NP_060725.1	Q6IA86-1
	ELP2	NM_001242875.3		c.83C>T	p.Pro28Leu	missense	Exon 1 of 23	NP_001229804.1	Q6IA86-6
	ELP2	NM_001324466.2		c.83C>T	p.Pro28Leu	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.83C>T	p.Pro28Leu	missense	Exon 1 of 22	ENSP00000350967.6	Q6IA86-1
	ELP2	ENST00000423854.6	TSL:1	c.83C>T	p.Pro28Leu	missense	Exon 1 of 19	ENSP00000391202.2	Q6IA86-7
	ELP2	ENST00000542824.5	TSL:1	c.83C>T	p.Pro28Leu	missense	Exon 1 of 20	ENSP00000443800.1	Q6IA86-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.047	D
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.58	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		0.49
PrimateAI	Benign	0.36	T
PROVEAN	Uncertain	-4.1	D
REVEL	Benign	0.12
Sift	Benign	0.066	T
Sift4G	Benign	0.24	T
Polyphen		0.078	B
Vest4		0.23
MutPred		0.63		Gain of MoRF binding (P = 0.0523)
MVP		0.71
MPC		0.096
ClinPred		0.98	D
GERP RS		3.7
PromoterAI		-0.16	Neutral
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

Other links and lift over

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