6-30889417-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_001297654.2(DDR1):c.404G>A(p.Arg135His) variant causes a missense change. The variant allele was found at a frequency of 0.0000181 in 1,550,850 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: 0.000017 ( 0 hom. )
Consequence
DDR1
NM_001297654.2 missense
NM_001297654.2 missense
Scores
5
9
4
Clinical Significance
Conservation
PhyloP100: 6.78
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.781
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DDR1 | NM_001297654.2 | c.404G>A | p.Arg135His | missense_variant | 4/18 | ENST00000376568.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DDR1 | ENST00000376568.8 | c.404G>A | p.Arg135His | missense_variant | 4/18 | 1 | NM_001297654.2 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152174Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000119 AC: 2AN: 168704Hom.: 0 AF XY: 0.0000110 AC XY: 1AN XY: 90544
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GnomAD4 exome AF: 0.0000172 AC: 24AN: 1398558Hom.: 0 Cov.: 32 AF XY: 0.0000189 AC XY: 13AN XY: 688674
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GnomAD4 genome AF: 0.0000263 AC: 4AN: 152292Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74458
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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 | Nov 04, 2023 | The c.404G>A (p.R135H) alteration is located in exon 3 (coding exon 3) of the DDR1 gene. This alteration results from a G to A substitution at nucleotide position 404, causing the arginine (R) at amino acid position 135 to be replaced by a histidine (H). 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
Uncertain
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
D;D;.;D;.;D;.;D;D;.;.;D;D;D;D;.;D;D;.;.;T;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;.;.;D;.;.;D;.;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;D;D;D;D;D
MetaSVM
Uncertain
D
MutationTaster
Benign
D;D;D;D;D;D;D;D;D;D;D;D
PrimateAI
Benign
T
PROVEAN
Uncertain
D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
REVEL
Uncertain
Sift
Benign
D;D;D;T;D;T;D;T;T;D;D;T;T;D;D;D;T;T;T;D;T;D;D
Sift4G
Benign
T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
Polyphen
0.084, 0.50, 0.57
.;B;.;.;.;.;.;.;.;.;.;.;.;B;B;.;.;.;.;.;.;P;P
Vest4
0.40, 0.36, 0.32, 0.35, 0.34, 0.40, 0.40, 0.40, 0.31, 0.32, 0.49, 0.38
MVP
MPC
0.70
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