rs863223537
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_001114753.3(ENG):c.562C>T(p.Gln188Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. Q188Q) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_001114753.3 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ENG | NM_001114753.3 | c.562C>T | p.Gln188Ter | stop_gained | 5/15 | ENST00000373203.9 | |
ENG | NM_000118.4 | c.562C>T | p.Gln188Ter | stop_gained | 5/14 | ||
ENG | NM_001278138.2 | c.16C>T | p.Gln6Ter | stop_gained | 5/15 | ||
ENG | NM_001406715.1 | c.562C>T | p.Gln188Ter | stop_gained | 5/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ENG | ENST00000373203.9 | c.562C>T | p.Gln188Ter | stop_gained | 5/15 | 1 | NM_001114753.3 | P2 | |
ENG | ENST00000344849.4 | c.562C>T | p.Gln188Ter | stop_gained | 5/14 | 1 | A2 | ||
ENG | ENST00000480266.6 | c.16C>T | p.Gln6Ter | stop_gained | 5/15 | 2 | |||
ENG | ENST00000462196.1 | n.462C>T | non_coding_transcript_exon_variant | 4/4 | 3 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1445698Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0AN XY: 717786
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
not provided Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Dec 21, 2021 | PM2, PS4_moderate, PVS1 - |
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Nov 02, 2016 | The Q188X pathogenic variant in the ENG gene has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge. Q188X is predicted to cause loss of normal protein function either by protein truncation or nonsense-mediated mRNA decay. Other nonsense variants in the ENG gene have been reported in association with HHT. In summary, Q188X in the ENG gene is interpreted as a pathogenic variant. This variant was found in HHT-PANCARD - |
Cardiovascular phenotype Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 09, 2022 | The p.Q188* pathogenic mutation (also known as c.562C>T), located in coding exon 5 of the ENG gene, results from a C to T substitution at nucleotide position 562. This changes the amino acid from a glutamine to a stop codon within coding exon 5. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. - |
Hereditary hemorrhagic telangiectasia Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Sep 07, 2018 | This sequence change creates a premature translational stop signal (p.Gln188*) in the ENG gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with ENG-related disease. ClinVar contains an entry for this variant (Variation ID: 213211). Loss-of-function variants in ENG are known to be pathogenic (PMID: 15879500, 20656886, 22385575). For these reasons, this variant has been classified as Pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at