19-18782917-A-G
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Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PM4
The NM_000095.3(COMP):āc.2272T>Cā(p.Ter758Glnext*?) variant causes a stop lost change. The variant allele was found at a frequency of 0.00000186 in 1,611,490 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.0000066 ( 0 hom., cov: 33)
Exomes š: 0.0000014 ( 0 hom. )
Consequence
COMP
NM_000095.3 stop_lost
NM_000095.3 stop_lost
Scores
2
5
Clinical Significance
Conservation
PhyloP100: 4.04
Genes affected
COMP (HGNC:2227): (cartilage oligomeric matrix protein) The protein encoded by this gene is a noncollagenous extracellular matrix (ECM) protein. It consists of five identical glycoprotein subunits, each with EGF-like and calcium-binding (thrombospondin-like) domains. Oligomerization results from formation of a five-stranded coiled coil and disulfides. Binding to other ECM proteins such as collagen appears to depend on divalent cations. Contraction or expansion of a 5 aa aspartate repeat and other mutations can cause pseudochondroplasia (PSACH) and multiple epiphyseal dysplasia (MED). [provided by RefSeq, Jul 2016]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PM4
Stoplost variant in NM_000095.3 Downstream stopcodon found after 67 codons.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
COMP | NM_000095.3 | c.2272T>C | p.Ter758Glnext*? | stop_lost | 19/19 | ENST00000222271.7 | NP_000086.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
COMP | ENST00000222271.7 | c.2272T>C | p.Ter758Glnext*? | stop_lost | 19/19 | 1 | NM_000095.3 | ENSP00000222271.2 | ||
COMP | ENST00000542601.6 | c.2173T>C | p.Ter725Glnext*? | stop_lost | 18/18 | 1 | ENSP00000439156.2 | |||
COMP | ENST00000425807.1 | c.2113T>C | p.Ter705Glnext*? | stop_lost | 18/18 | 2 | ENSP00000403792.1 |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 152080Hom.: 0 Cov.: 33
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GnomAD4 exome AF: 0.00000137 AC: 2AN: 1459410Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 726130
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GnomAD4 genome AF: 0.00000658 AC: 1AN: 152080Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74292
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
COMP-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 28, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. - |
Computational scores
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BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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Uncertain
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Uncertain
FATHMM_MKL
Benign
N
Vest4
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at