6-30892360-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001297654.2(DDR1):​c.917G>C​(p.Arg306Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R306W) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Consequence

DDR1
NM_001297654.2 missense

Scores

1
6
12

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.26
Variant links:
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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.25393093).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DDR1NM_001297654.2 linkc.917G>C p.Arg306Pro missense_variant Exon 8 of 18 ENST00000376568.8 NP_001284583.1 Q08345-1A0A024RCL1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DDR1ENST00000376568.8 linkc.917G>C p.Arg306Pro missense_variant Exon 8 of 18 1 NM_001297654.2 ENSP00000365752.3 Q08345-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.85
BayesDel_addAF
Benign
-0.079
T
BayesDel_noAF
Benign
-0.35
CADD
Benign
22
DANN
Uncertain
0.98
DEOGEN2
Benign
0.18
T;.;.;.;.;T;T;.;.;T;.;T
Eigen
Benign
-0.40
Eigen_PC
Benign
-0.37
FATHMM_MKL
Uncertain
0.86
D
LIST_S2
Uncertain
0.90
.;.;.;.;.;.;.;.;.;.;D;.
M_CAP
Benign
0.035
D
MetaRNN
Benign
0.25
T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.1
L;L;L;L;L;L;L;.;L;.;L;.
PrimateAI
Uncertain
0.63
T
PROVEAN
Benign
-1.8
N;N;N;N;N;N;N;N;N;.;N;D
REVEL
Benign
0.12
Sift
Uncertain
0.014
D;D;D;D;D;D;D;D;D;.;D;D
Sift4G
Uncertain
0.026
D;D;D;D;D;D;D;D;D;D;D;D
Polyphen
0.0010
B;.;.;.;.;B;B;.;.;.;P;D
Vest4
0.55
MutPred
0.44
Loss of MoRF binding (P = 0.0036);Loss of MoRF binding (P = 0.0036);Loss of MoRF binding (P = 0.0036);Loss of MoRF binding (P = 0.0036);Loss of MoRF binding (P = 0.0036);Loss of MoRF binding (P = 0.0036);Loss of MoRF binding (P = 0.0036);.;Loss of MoRF binding (P = 0.0036);Loss of MoRF binding (P = 0.0036);Loss of MoRF binding (P = 0.0036);.;
MVP
0.58
ClinPred
0.64
D
GERP RS
2.1
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.87
gMVP
0.86

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-30860137; API