Variant rs770421290 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001297654.2(DDR1):c.182A>C(p.His61Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,734 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: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

DDR1
NM_001297654.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.14

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]

DDR1 links:

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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, 0.906

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDR1	NM_001297654.2 link	c.182A>C	p.His61Pro	missense_variant	Exon 3 of 18	ENST00000376568.8	NP_001284583.1	Q08345-1A0A024RCL1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDR1	ENST00000376568.8 link	c.182A>C	p.His61Pro	missense_variant	Exon 3 of 18	1	NM_001297654.2	ENSP00000365752.3		Q08345-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000406

AC:

AN:

246424

Hom.:

AF XY:

0.00000744

AC XY:

AN XY:

134322

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000329

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460734

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726682

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000846

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.97

BayesDel_addAF

Pathogenic

0.45

BayesDel_noAF

Pathogenic

0.51

CADD

Pathogenic

DANN

Uncertain

0.98

DEOGEN2

Uncertain

0.66

D;D;D;.;.;.;T;T;.;D;.;D;T;.;D;.;D;.;.;D;D;D;D;.;T;D;D;D;.;.;T;.;.

Eigen

Uncertain

0.61

Eigen_PC

Uncertain

0.57

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.86

D;D;.;D;D;.;D;D;D;D;.;.;D;D;.;D;D;.;.;D;D;.;.;.;D;.;D;D;D;.;.;.;D

M_CAP

Pathogenic

0.79

MetaRNN

Pathogenic

0.91

D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D

MetaSVM

Pathogenic

1.1

MutationAssessor

Uncertain

2.3

.;.;M;.;.;M;.;.;.;.;M;.;.;.;.;.;.;M;M;.;.;M;M;.;.;.;.;.;.;M;.;M;M

PrimateAI

Uncertain

0.51

PROVEAN

Pathogenic

-7.2

D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D

REVEL

Pathogenic

0.94

Sift

Uncertain

0.0020

D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D

Sift4G

Uncertain

0.028

D;T;D;D;D;D;D;D;D;T;D;T;D;T;T;D;T;D;D;T;T;D;D;D;D;T;T;D;T;D;D;T;D

Polyphen

1.0, 1.0, 1.0

.;.;D;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;D;D;.;.;.;.;.;.;.;.;D;D

Vest4

0.64, 0.63, 0.59, 0.62, 0.63, 0.64, 0.62, 0.48, 0.64, 0.76, 0.63

MutPred

0.65

Gain of glycosylation at S62 (P = 0.0871);Gain of glycosylation at S62 (P = 0.0871);Gain of glycosylation at S62 (P = 0.0871);Gain of glycosylation at S62 (P = 0.0871);Gain of glycosylation at S62 (P = 0.0871);Gain of glycosylation at S62 (P = 0.0871);Gain of glycosylation at S62 (P = 0.0871);Gain of glycosylation at S62 (P = 0.0871);Gain of glycosylation at S62 (P = 0.0871);Gain of glycosylation at S62 (P = 0.0871);Gain of glycosylation at S62 (P = 0.0871);Gain of glycosylation at S62 (P = 0.0871);Gain of glycosylation at S62 (P = 0.0871);Gain of glycosylation at S62 (P = 0.0871);Gain of glycosylation at S62 (P = 0.0871);Gain of glycosylation at S62 (P = 0.0871);Gain of glycosylation at S62 (P = 0.0871);Gain of glycosylation at S62 (P = 0.0871);Gain of glycosylation at S62 (P = 0.0871);Gain of glycosylation at S62 (P = 0.0871);Gain of glycosylation at S62 (P = 0.0871);Gain of glycosylation at S62 (P = 0.0871);Gain of glycosylation at S62 (P = 0.0871);.;Gain of glycosylation at S62 (P = 0.0871);Gain of glycosylation at S62 (P = 0.0871);Gain of glycosylation at S62 (P = 0.0871);Gain of glycosylation at S62 (P = 0.0871);.;Gain of glycosylation at S62 (P = 0.0871);Gain of glycosylation at S62 (P = 0.0871);Gain of glycosylation at S62 (P = 0.0871);Gain of glycosylation at S62 (P = 0.0871);

MVP

0.96

MPC

1.7

ClinPred

0.96

GERP RS

5.1

Varity_R

0.93

gMVP

0.93

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over