dbSNP rs9468843: DDR1:c.*885T>C (chr6-30900181-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001297654.2(DDR1):c.*885T>C variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 508,590 control chromosomes in the GnomAD database, including 14,765 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.17 ( 2925 hom., cov: 32)

Exomes 𝑓: 0.23 ( 11840 hom. )

Consequence

DDR1
NM_001297654.2 downstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.23

Publications

13 publications found

Variant links:

COSMIC-nc: COSV61319151

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 Gene-Disease associations (from GenCC):

chondrodysplasia
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

DDR1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.385 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDR1	NM_001297654.2 link	c.*885T>C		downstream_gene_variant		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.*885T>C		downstream_gene_variant		1	NM_001297654.2	ENSP00000365752.3		Q08345-1

Frequencies

GnomAD3 genomes

AF:

0.173

AC:

26340

AN:

152006

Hom.:

2910

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0880

Gnomad AMI

AF:

0.292

Gnomad AMR

AF:

0.295

Gnomad ASJ

AF:

0.203

Gnomad EAS

AF:

0.371

Gnomad SAS

AF:

0.401

Gnomad FIN

AF:

0.223

Gnomad MID

AF:

0.158

Gnomad NFE

AF:

0.156

Gnomad OTH

AF:

0.172

GnomAD4 exome

AF:

0.227

AC:

80751

AN:

356466

Hom.:

11840

Cov.:

AF XY:

0.236

AC XY:

46307

AN XY:

196526

show subpopulations

African (AFR)

AF:

0.0867

AC:

922

AN:

10640

American (AMR)

AF:

0.391

AC:

11347

AN:

29014

Ashkenazi Jewish (ASJ)

AF:

0.204

AC:

2474

AN:

12120

East Asian (EAS)

AF:

0.394

AC:

7908

AN:

20076

South Asian (SAS)

AF:

0.374

AC:

20749

AN:

55430

European-Finnish (FIN)

AF:

0.218

AC:

3214

AN:

14770

Middle Eastern (MID)

AF:

0.175

AC:

502

AN:

2870

European-Non Finnish (NFE)

AF:

0.154

AC:

29814

AN:

193056

Other (OTH)

AF:

0.207

AC:

3821

AN:

18490

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

2819

5638

8458

11277

14096

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

494

988

1482

1976

2470

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.173

AC:

26369

AN:

152124

Hom.:

2925

Cov.:

AF XY:

0.184

AC XY:

13687

AN XY:

74360

show subpopulations

African (AFR)

AF:

0.0878

AC:

3646

AN:

41528

American (AMR)

AF:

0.295

AC:

4514

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.203

AC:

704

AN:

3466

East Asian (EAS)

AF:

0.372

AC:

1917

AN:

5158

South Asian (SAS)

AF:

0.400

AC:

1923

AN:

4808

European-Finnish (FIN)

AF:

0.223

AC:

2364

AN:

10580

Middle Eastern (MID)

AF:

0.160

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.156

AC:

10608

AN:

67996

Other (OTH)

AF:

0.180

AC:

380

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1069

2138

3207

4276

5345

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

296

592

888

1184

1480

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.163

Hom.:

6004

Bravo

AF:

0.171

Asia WGS

AF:

0.439

AC:

1526

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

7.4

(source)

DANN

Benign

0.46

PhyloP100

2.2

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over