rs1437728449
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_001297654.2(DDR1):c.470C>A(p.Pro157His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,206 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Consequence
DDR1
NM_001297654.2 missense
NM_001297654.2 missense
Scores
13
5
1
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 7.56
Genes affected
DDR1 (HGNC:2730): (discoidin domain receptor tyrosine kinase 1) Receptor tyrosine kinases play a key role in the communication of cells with their microenvironment. These kinases are involved in the regulation of cell growth, differentiation and metabolism. The protein encoded by this gene belongs to a subfamily of tyrosine kinase receptors with homology to Dictyostelium discoideum protein discoidin I in their extracellular domain, and that are activated by various types of collagen. Expression of this protein is restricted to epithelial cells, particularly in the kidney, lung, gastrointestinal tract, and brain. In addition, it has been shown to be significantly overexpressed in several human tumors. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Feb 2011]
MIR4640 (HGNC:41561): (microRNA 4640) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]
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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;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.903
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| DDR1 | NM_001297654.2 | c.470C>A | p.Pro157His | missense_variant | Exon 5 of 18 | ENST00000376568.8 | NP_001284583.1 |
Ensembl
Frequencies
GnomAD3 genomes 0.00000657 AC: 1AN: 152206Hom.: 0 Cov.: 32
GnomAD3 genomes
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GnomAD4 exome Cov.: 33
GnomAD4 exome
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33
GnomAD4 genome 0.00000657 AC: 1AN: 152206Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74354
GnomAD4 genome
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32
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74354
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ClinVar
Not reported inComputational scores
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Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
D;D;.;.;.;.;.;D;D;D;D;.;D;.;.;T;.;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;.;.;.;D;.;.;D;D;.;.;.;.;D;.;.;.;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM
Pathogenic
D
MutationAssessor
Uncertain
.;M;M;M;.;M;M;.;.;M;M;.;.;.;M;.;M;M
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
REVEL
Pathogenic
Sift
Pathogenic
D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
Sift4G
Uncertain
D;D;D;D;T;D;D;D;D;D;D;D;T;D;D;D;T;D
Polyphen
1.0
.;D;.;.;.;.;.;.;.;D;D;.;.;.;.;.;D;D
Vest4
0.86, 0.69, 0.69, 0.72, 0.72, 0.85, 0.85, 0.65, 0.79, 0.70, 0.84
MutPred
Loss of ubiquitination at K153 (P = 0.0474);Loss of ubiquitination at K153 (P = 0.0474);Loss of ubiquitination at K153 (P = 0.0474);Loss of ubiquitination at K153 (P = 0.0474);Loss of ubiquitination at K153 (P = 0.0474);Loss of ubiquitination at K153 (P = 0.0474);Loss of ubiquitination at K153 (P = 0.0474);Loss of ubiquitination at K153 (P = 0.0474);Loss of ubiquitination at K153 (P = 0.0474);Loss of ubiquitination at K153 (P = 0.0474);Loss of ubiquitination at K153 (P = 0.0474);.;Loss of ubiquitination at K153 (P = 0.0474);.;Loss of ubiquitination at K153 (P = 0.0474);Loss of ubiquitination at K153 (P = 0.0474);Loss of ubiquitination at K153 (P = 0.0474);Loss of ubiquitination at K153 (P = 0.0474);
MVP
MPC
1.5
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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