rs1554809331
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001114753.3(ENG):c.1415_1417delinsGT(p.Gln472ArgfsTer19) 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 (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Consequence
ENG
NM_001114753.3 frameshift
NM_001114753.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 1.24
Genes affected
ENG (HGNC:3349): (endoglin) This gene encodes a homodimeric transmembrane protein which is a major glycoprotein of the vascular endothelium. This protein is a component of the transforming growth factor beta receptor complex and it binds to the beta1 and beta3 peptides with high affinity. Mutations in this gene cause hereditary hemorrhagic telangiectasia, also known as Osler-Rendu-Weber syndrome 1, an autosomal dominant multisystemic vascular dysplasia. This gene may also be involved in preeclampsia and several types of cancer. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2013]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 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 9-127818727-TCT-AC is Pathogenic according to our data. Variant chr9-127818727-TCT-AC is described in ClinVar as [Pathogenic]. Clinvar id is 528066.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ENG | NM_001114753.3 | c.1415_1417delinsGT | p.Gln472ArgfsTer19 | frameshift_variant | 11/15 | ENST00000373203.9 | |
LOC102723566 | NR_136302.1 | n.1568+16_1568+18delinsAC | intron_variant, non_coding_transcript_variant | ||||
ENG | NM_000118.4 | c.1415_1417delinsGT | p.Gln472ArgfsTer19 | frameshift_variant | 11/14 | ||
ENG | NM_001278138.2 | c.869_871delinsGT | p.Gln290ArgfsTer19 | frameshift_variant | 11/15 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ENG | ENST00000373203.9 | c.1415_1417delinsGT | p.Gln472ArgfsTer19 | frameshift_variant | 11/15 | 1 | NM_001114753.3 | P2 | |
ENST00000439298.5 | n.1568+16_1568+18delinsAC | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Hereditary hemorrhagic telangiectasia Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Nov 18, 2017 | For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in ENG are known to be pathogenic (PMID: 15879500, 20656886, 22385575). This variant has been reported in several individuals affected with hereditary hemorrhagic telangiectasia (PMID: 10625079, 15907823, 17384219). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Gln472Argfs*19) in the ENG gene. It is expected to result in an absent or disrupted protein product. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at