chr9-23701494-C-G

Variant names:

• chr9-23701494-C-G
• NM_004432.5:c.598G>C

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_004432.5(ELAVL2):​c.598G>C​(p.Val200Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ELAVL2 NM_004432.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.57
• Publications: 0 publications found

Genes affected

ELAVL2 (HGNC:3313): (ELAV like RNA binding protein 2) In humans, the ELAV like RNA binding protein gene family has four members (ELAVL1-4). ELAVL RNA binding proteins recognize AU-rich elements in the 3' UTRs of gene transcripts and thereby regulate gene expression post-transcriptionally. The protein encoded by this gene binds to several 3' UTRs, including its own and also that of FOS, ID, and POU5F1. This gene encodes ELAVL2 and, like ELAVL3 and ELAVL4, is expressed specifically in neurons and primarily localizes to the cytoplasm. This protein also forms a cytosolic complex with the normally nuclear-localized ELAVL1 protein. Alternative splicing of this gene results in multiple transcript variants encoding distinct protein isoforms. [provided by RefSeq, Jul 2020]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.815

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004432.5. 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
	ELAVL2	NM_004432.5	MANE Select	c.598G>C	p.Val200Leu	missense	Exon 5 of 7	NP_004423.2	Q12926-1
	ELAVL2	NM_001351455.2		c.685G>C	p.Val229Leu	missense	Exon 6 of 8	NP_001338384.1	A0A0A0MRX1
	ELAVL2	NM_001385697.1		c.685G>C	p.Val229Leu	missense	Exon 6 of 8	NP_001372626.1	A0A0A0MRX1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELAVL2	ENST00000397312.7	TSL:1 MANE Select	c.598G>C	p.Val200Leu	missense	Exon 5 of 7	ENSP00000380479.2	Q12926-1
	ELAVL2	ENST00000380117.5	TSL:1	c.598G>C	p.Val200Leu	missense	Exon 5 of 7	ENSP00000369460.1	Q12926-1
	ELAVL2	ENST00000223951.10	TSL:1	c.598G>C	p.Val200Leu	missense	Exon 5 of 6	ENSP00000223951.5	Q12926-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.29	D
BayesDel_noAF	Pathogenic	0.18
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T
Eigen	Pathogenic	0.73
Eigen_PC	Pathogenic	0.77
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Benign	0.034	D
MetaRNN	Pathogenic	0.81	D
MetaSVM	Benign	-0.41	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		7.6
PrimateAI	Pathogenic	0.90	D
PROVEAN	Uncertain	-2.8	D
REVEL	Uncertain	0.43
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0020	D
Polyphen		0.70	P
Vest4		0.85
MutPred		0.61		Gain of ubiquitination at K201 (P = 0.1418)
MVP		0.86
MPC		0.91
ClinPred		0.97	D
GERP RS		5.9
Varity_R		0.68
gMVP		0.67
Mutation Taster		=37/63	disease causing

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: chr9-23701492;