6-30889296-C-T

Variant names:

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001297654.2(DDR1):c.283C>T(p.His95Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.0000242 in 1,612,776 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 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000025 ( 0 hom. )

Consequence

DDR1
NM_001297654.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.12

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:

Genome browser will be placed here

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, 0.752

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDR1	NM_001297654.2 link	c.283C>T	p.His95Tyr	missense_variant	Exon 4 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.283C>T	p.His95Tyr	missense_variant	Exon 4 of 18	1	NM_001297654.2	ENSP00000365752.3		Q08345-1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000487

AC:

AN:

246452

Hom.:

AF XY:

0.0000670

AC XY:

AN XY:

134346

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:

0.000395

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000246

AC:

AN:

1460632

Hom.:

Cov.:

AF XY:

0.0000358

AC XY:

AN XY:

726630

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:

0.000417

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152144

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000102

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000594

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 25, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.283C>T (p.H95Y) alteration is located in exon 3 (coding exon 3) of the DDR1 gene. This alteration results from a C to T substitution at nucleotide position 283, causing the histidine (H) at amino acid position 95 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Pathogenic

0.23

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.64

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

Eigen

Uncertain

0.55

Eigen_PC

Uncertain

0.54

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.92

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

M_CAP

Uncertain

0.27

MetaRNN

Pathogenic

0.75

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

Benign

1.4

.;.;L;.;.;L;.;.;L;.;.;.;.;L;L;.;.;L;L;.;.;.;.;.;.;L;.;L;L

PrimateAI

Uncertain

0.66

PROVEAN

Uncertain

-4.0

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

0.80

Sift

Uncertain

0.016

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

Sift4G

Benign

0.17

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

Polyphen

1.0, 1.0

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

Vest4

0.81, 0.69, 0.63, 0.68, 0.73, 0.81, 0.81, 0.81, 0.62, 0.80, 0.65

MutPred

0.59

Loss of catalytic residue at R93 (P = 0.0884);Loss of catalytic residue at R93 (P = 0.0884);Loss of catalytic residue at R93 (P = 0.0884);Loss of catalytic residue at R93 (P = 0.0884);Loss of catalytic residue at R93 (P = 0.0884);Loss of catalytic residue at R93 (P = 0.0884);Loss of catalytic residue at R93 (P = 0.0884);Loss of catalytic residue at R93 (P = 0.0884);Loss of catalytic residue at R93 (P = 0.0884);Loss of catalytic residue at R93 (P = 0.0884);Loss of catalytic residue at R93 (P = 0.0884);Loss of catalytic residue at R93 (P = 0.0884);Loss of catalytic residue at R93 (P = 0.0884);Loss of catalytic residue at R93 (P = 0.0884);Loss of catalytic residue at R93 (P = 0.0884);Loss of catalytic residue at R93 (P = 0.0884);Loss of catalytic residue at R93 (P = 0.0884);Loss of catalytic residue at R93 (P = 0.0884);Loss of catalytic residue at R93 (P = 0.0884);.;Loss of catalytic residue at R93 (P = 0.0884);Loss of catalytic residue at R93 (P = 0.0884);Loss of catalytic residue at R93 (P = 0.0884);Loss of catalytic residue at R93 (P = 0.0884);.;Loss of catalytic residue at R93 (P = 0.0884);Loss of catalytic residue at R93 (P = 0.0884);Loss of catalytic residue at R93 (P = 0.0884);Loss of catalytic residue at R93 (P = 0.0884);

MVP

0.96

MPC

1.5

ClinPred

0.70

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.77

gMVP

0.80

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over