chr11-726480-C-CCGCG

Variant names:

• chr11-726480-C-CCGCG
• ENST00000318562.13:c.1921_1922insCGCG

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PVS1_Moderate PM2

The NM_022772.4(EPS8L2):​c.1931_1934dupCGCG variant causes a splice donor, intron 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.

• Frequency: Genomes: not found (cov: 33)
• Consequence: EPS8L2 NM_022772.4 splice_donor, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.736

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]

ENSG00000269915 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PVS1: Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.084264435 fraction of the gene. Cryptic splice site detected, with MaxEntScore 8, offset of 0 (no position change), new splice context is: gcgGTgagc. Cryptic site results in inframe change. If cryptic site found is not functional and variant results in exon loss, it results in frameshift change.
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPS8L2	NM_022772.4	c.1931_1934dupCGCG		splice_donor_variant, intron_variant	Intron 19 of 20	ENST00000318562.13	NP_073609.2
EPS8L2	XM_017018132.2	c.1931_1934dupCGCG		splice_donor_variant, intron_variant	Intron 20 of 21		XP_016873621.1
EPS8L2	XM_047427411.1	c.1931_1934dupCGCG		splice_donor_variant, intron_variant	Intron 20 of 21		XP_047283367.1
EPS8L2	XM_047427412.1	c.1394_1397dupCGCG		splice_donor_variant, intron_variant	Intron 14 of 15		XP_047283368.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPS8L2	ENST00000318562.13	c.1921_1922insCGCG	p.Phe642AlafsTer126	frameshift_variant	Exon 19 of 21	1	NM_022772.4	ENSP00000320828.8

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-726480;