3-184276991-GGC-TCA

Variant names:

• chr3-184276991-GGC-TCA
• NM_001100121.2:c.226_228delGGCinsTCA
• ECE2 p.Gly76Ser

Variant summary

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

The NM_001100121.2(ECE2):​c.226_228delGGCinsTCA​(p.Gly76Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ECE2 NM_001100121.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.47
• Publications: 0 publications found

Genes affected

ECE2 (HGNC:13275): (endothelin converting enzyme 2) Enables metalloendopeptidase activity. Involved in peptide hormone processing. Located in cytoplasmic vesicle membrane. [provided by Alliance of Genome Resources, Apr 2022]

EEF1AKMT4-ECE2 (HGNC:53615): (EEF1AKMT4-ECE2 readthrough) This gene represents naturally occurring readthrough transcription between adjacent genes eukaryotic translation elongation factor 1 alpha lysine methyltransferase 4 (GeneID: 110599564) and endothelin converting enzyme 2 (GeneID:9718). The readthrough transcript representing this gene encodes a fusion protein that shares sequence identity with each individual gene product. [provided by RefSeq, Jul 2017]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001100121.2. 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
	ECE2	NM_001100121.2	MANE Select	c.226_228delGGCinsTCA	p.Gly76Ser	missense	N/A	NP_001093591.1	P0DPD6-2
	EEF1AKMT4-ECE2	NM_014693.4		c.580_582delGGCinsTCA	p.Gly194Ser	missense	N/A	NP_055508.3
	ECE2	NM_001100120.2		c.364_366delGGCinsTCA	p.Gly122Ser	missense	N/A	NP_001093590.1	P0DPD6-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ECE2	ENST00000404464.8	TSL:1 MANE Select	c.226_228delGGCinsTCA	p.Gly76Ser	missense	N/A	ENSP00000385846.3	P0DPD6-2
	EEF1AKMT4-ECE2	ENST00000402825.7	TSL:1	c.580_582delGGCinsTCA	p.Gly194Ser	missense	N/A	ENSP00000384223.3	P0DPD8-1
	ECE2	ENST00000357474.9	TSL:1	c.364_366delGGCinsTCA	p.Gly122Ser	missense	N/A	ENSP00000350066.5	P0DPD6-4

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.5

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr3-183994779;