chr6-56069062-C-T
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Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_030820.4(COL21A1):c.2075G>A(p.Gly692Glu) variant causes a missense change. The variant allele was found at a frequency of 0.0000494 in 1,600,476 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000052 ( 0 hom. )
Consequence
COL21A1
NM_030820.4 missense
NM_030820.4 missense
Scores
13
5
1
Clinical Significance
Conservation
PhyloP100: 4.59
Genes affected
COL21A1 (HGNC:17025): (collagen type XXI alpha 1 chain) This gene encodes the alpha chain of type XXI collagen, a member of the FACIT (fibril-associated collagens with interrupted helices) collagen family. Type XXI collagen is localized to tissues containing type I collagen and maintains the integrity of the extracellular matrix. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.989
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL21A1 | NM_030820.4 | c.2075G>A | p.Gly692Glu | missense_variant | 22/30 | ENST00000244728.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL21A1 | ENST00000244728.10 | c.2075G>A | p.Gly692Glu | missense_variant | 22/30 | 1 | NM_030820.4 | A1 |
Frequencies
GnomAD3 genomes AF: 0.0000264 AC: 4AN: 151428Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000465 AC: 11AN: 236536Hom.: 0 AF XY: 0.0000312 AC XY: 4AN XY: 128308
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GnomAD4 exome AF: 0.0000518 AC: 75AN: 1449048Hom.: 0 Cov.: 29 AF XY: 0.0000444 AC XY: 32AN XY: 720426
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GnomAD4 genome AF: 0.0000264 AC: 4AN: 151428Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 73892
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 12, 2021 | The c.2075G>A (p.G692E) alteration is located in exon 22 (coding exon 21) of the COL21A1 gene. This alteration results from a G to A substitution at nucleotide position 2075, causing the glycine (G) at amino acid position 692 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
D;.;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D
MetaSVM
Pathogenic
D
MutationAssessor
Pathogenic
H;.;.
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;.
REVEL
Pathogenic
Sift
Uncertain
D;D;.
Sift4G
Pathogenic
D;D;D
Polyphen
D;.;.
Vest4
MutPred
Gain of solvent accessibility (P = 0.0062);.;.;
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at