chr2-188994037-GGGCCCTCCTGGGATTAA-CCGTCCTGGGCCCTGGTGGTATACAAACCTGGTATACCACC
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PVS1_ModeratePM2PP3PP5
The NM_000090.4(COL3A1):c.1150-1_1166delinsCCGTCCTGGGCCCTGGTGGTATACAAACCTGGTATACCACC variant causes a splice acceptor, coding sequence change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 32)
Consequence
COL3A1
NM_000090.4 splice_acceptor, coding_sequence
NM_000090.4 splice_acceptor, coding_sequence
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 9.55
Genes affected
COL3A1 (HGNC:2201): (collagen type III alpha 1 chain) This gene encodes the pro-alpha1 chains of type III collagen, a fibrillar collagen that is found in extensible connective tissues such as skin, lung, uterus, intestine and the vascular system, frequently in association with type I collagen. Mutations in this gene are associated with Ehlers-Danlos syndrome type IV, and with aortic and arterial aneurysms. [provided by R. Dalgleish, Feb 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
PVS1
Splicing variant, NOT destroyed by nmd, known LOF gene, truncates exone, which is 0.0049988637 fraction of the gene. No cryptic splice site detected. Exon removal is inframe change.
PM2
Very rare variant in population databases, with high coverage;
PP3
No computational evidence supports a deleterious effect, but strongly conserved according to phyloP
PP5
Variant 2-188994037-GGGCCCTCCTGGGATTAA-CCGTCCTGGGCCCTGGTGGTATACAAACCTGGTATACCACC is Pathogenic according to our data. Variant chr2-188994037-GGGCCCTCCTGGGATTAA-CCGTCCTGGGCCCTGGTGGTATACAAACCTGGTATACCACC is described in ClinVar as [Pathogenic]. Clinvar id is 101332.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL3A1 | NM_000090.4 | c.1150-1_1166delinsCCGTCCTGGGCCCTGGTGGTATACAAACCTGGTATACCACC | splice_acceptor_variant, coding_sequence_variant | 17/51 | ENST00000304636.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL3A1 | ENST00000304636.9 | c.1150-1_1166delinsCCGTCCTGGGCCCTGGTGGTATACAAACCTGGTATACCACC | splice_acceptor_variant, coding_sequence_variant | 17/51 | 1 | NM_000090.4 | P1 | ||
COL3A1 | ENST00000450867.2 | c.1051-1_1067delinsCCGTCCTGGGCCCTGGTGGTATACAAACCTGGTATACCACC | splice_acceptor_variant, coding_sequence_variant | 16/50 | 1 |
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: no assertion criteria provided
LINK: link
Submissions by phenotype
Ehlers-Danlos syndrome, type 4 Pathogenic:1
Pathogenic, no assertion criteria provided | clinical testing | Collagen Diagnostic Laboratory, University of Washington | - | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at