rs1554952193

Positions:

• chr11-721320-GC-G

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_022772.4(EPS8L2):​c.738del​(p.Val247CysfsTer6) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 33)
• Consequence: EPS8L2 NM_022772.4 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 2.57

Genes affected

EPS8L2 (HGNC:21296): (EPS8 signaling adaptor L2) This gene encodes a member of the EPS8 gene family. The encoded protein, like other members of the family, is thought to link growth factor stimulation to actin organization, generating functional redundancy in the pathways that regulate actin cytoskeletal remodeling. [provided by RefSeq, Dec 2008]

(HGNC:):

ACMG classification

Verdict is Pathogenic. Variant got 11 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 11-721320-GC-G is Pathogenic according to our data. Variant chr11-721320-GC-G is described in ClinVar as [Pathogenic]. Clinvar id is 433530.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPS8L2	NM_022772.4	c.738del	p.Val247CysfsTer6	frameshift_variant	9/21	ENST00000318562.13	NP_073609.2
EPS8L2	XM_017018132.2	c.738del	p.Val247CysfsTer6	frameshift_variant	10/22		XP_016873621.1
EPS8L2	XM_047427411.1	c.738del	p.Val247CysfsTer6	frameshift_variant	10/22		XP_047283367.1
EPS8L2	XM_047427412.1	c.201del	p.Val68CysfsTer6	frameshift_variant	4/16		XP_047283368.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPS8L2	ENST00000318562.13	c.738del	p.Val247CysfsTer6	frameshift_variant	9/21	1	NM_022772.4	ENSP00000320828	P1
	ENST00000527021.2	n.72+5655del		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Hearing loss, autosomal recessive 106 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Aug 23, 2017

- -

Computational scores

Source: dbNSFP v4.3

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: rs1554952193; hg19: chr11-721320;