chr18-36129968-T-C

Variant names:

• chr18-36129968-T-C
• rs920708444
• NM_018255.4:c.35T>C

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 2 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 1 ACMG points.

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

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.35T>C	p.Phe12Ser	missense	Exon 1 of 22	NP_060725.1	Q6IA86-1
	ELP2	NM_001242875.3		c.35T>C	p.Phe12Ser	missense	Exon 1 of 23	NP_001229804.1	Q6IA86-6
	ELP2	NM_001324466.2		c.35T>C	p.Phe12Ser	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.35T>C	p.Phe12Ser	missense	Exon 1 of 22	ENSP00000350967.6	Q6IA86-1
	ELP2	ENST00000423854.6	TSL:1	c.35T>C	p.Phe12Ser	missense	Exon 1 of 19	ENSP00000391202.2	Q6IA86-7
	ELP2	ENST00000542824.5	TSL:1	c.35T>C	p.Phe12Ser	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 as Germline

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	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
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.32	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.70	N
PhyloP100		2.4
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-0.94	N
REVEL	Benign	0.22
Sift	Benign	0.70	T
Sift4G	Benign	0.60	T
Polyphen		0.12	B
Vest4		0.80
MutPred		0.68		Gain of disorder (P = 0.0238)
MVP		0.33
MPC		0.16
ClinPred		0.56	D
GERP RS		5.6
PromoterAI		0.019	Neutral
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.9
Varity_R		0.36
gMVP		0.61
Mutation Taster		=91/9	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: rs920708444; hg19: chr18-33709931;