12-15681305-GTAATAATAATAATAA-GTAATAATAATAATAATAATAATAATAATAATAATAATAA

Variant names:

• chr12-15681305-G-GTAATAATAATAATAATAATAATAA
• NM_004447.6:c.60-27_60-4dupTTATTATTATTATTATTATTATTA

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_004447.6(EPS8):​c.60-27_60-4dupTTATTATTATTATTATTATTATTA variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000107 in 936,860 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 27)
  • Exomes 𝑓: 0.0000011 (0 hom.)
• Consequence: EPS8 NM_004447.6 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.197

Genes affected

EPS8 (HGNC:3420): (EGFR pathway substrate 8, signaling adaptor) This gene encodes a member of the EPS8 family. This protein contains one PH domain and one SH3 domain. It functions as part of the EGFR pathway, though its exact role has not been determined. Highly similar proteins in other organisms are involved in the transduction of signals from Ras to Rac and growth factor-mediated actin remodeling. Alternate transcriptional splice variants of this gene have been observed but have not been thoroughly characterized. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPS8	NM_004447.6	c.60-27_60-4dupTTATTATTATTATTATTATTATTA		splice_region_variant, intron_variant	Intron 2 of 20	ENST00000281172.10	NP_004438.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPS8	ENST00000281172.10	c.60-4_60-3insTTATTATTATTATTATTATTATTA		splice_region_variant, intron_variant	Intron 2 of 20	1	NM_004447.6	ENSP00000281172.5

Frequencies

GnomAD3 genomes Cov.: 27

GnomAD4 exome AF: 0.00000107 AC: 1 AN: 936860 Hom.: 0 Cov.: 11 AF XY: 0.00 AC XY: 0 AN XY: 471864

Gnomad4 AFR exome AF: 0.0000592

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 27

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: chr12-15834239;