rs2298258

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP6_Very_StrongBP7BA1

The NM_006182.4(DDR2):c.1260C>G(p.Leu420Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 1,613,736 control chromosomes in the GnomAD database, including 35,769 homozygotes. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. L420L) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.26 ( 6952 hom., cov: 32)

Exomes 𝑓: 0.18 ( 28817 hom. )

Consequence

DDR2
NM_006182.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.244

Publications

24 publications found

Variant links:

Genes affected

DDR2 (HGNC:2731): (discoidin domain receptor tyrosine kinase 2) This gene encodes a member of the discoidin domain receptor subclass of the receptor tyrosine kinase (RTKs) protein family. RTKs play a key role in the communication of cells with their microenvironment. The encoded protein is a collagen-induced receptor that activates signal transduction pathways involved in cell adhesion, proliferation, and extracellular matrix remodeling. This protein is expressed in numerous cell types and may alos be involved in wound repair and regulate tumor growth and invasiveness. Mutations in this gene are the cause of short limb-hand type spondylometaepiphyseal dysplasia. [provided by RefSeq, Aug 2017]

DDR2 Gene-Disease associations (from GenCC):

spondyloepimetaphyseal dysplasia-short limb-abnormal calcification syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae), G2P, Orphanet
warburg-cinotti syndrome
Inheritance: Unknown, AD Classification: STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, G2P, Illumina, Ambry Genetics

DDR2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -17 ACMG points.

BP6

Variant 1-162767326-C-G is Benign according to our data. Variant chr1-162767326-C-G is described in ClinVar as Benign. ClinVar VariationId is 259929.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.244 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.47 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006182.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
DDR2	NM_006182.4	MANE Select	c.1260C>G	p.Leu420Leu	synonymous	Exon 11 of 18	NP_006173.2
DDR2	NM_001014796.3		c.1260C>G	p.Leu420Leu	synonymous	Exon 12 of 19	NP_001014796.1
DDR2	NM_001354982.2		c.1260C>G	p.Leu420Leu	synonymous	Exon 11 of 18	NP_001341911.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
DDR2	ENST00000367921.8	TSL:1 MANE Select	c.1260C>G	p.Leu420Leu	synonymous	Exon 11 of 18	ENSP00000356898.3
DDR2	ENST00000367922.7	TSL:1	c.1260C>G	p.Leu420Leu	synonymous	Exon 12 of 19	ENSP00000356899.2
DDR2	ENST00000877159.1		c.1260C>G	p.Leu420Leu	synonymous	Exon 11 of 18	ENSP00000547218.1

Frequencies

GnomAD3 genomes

AF:

0.260

AC:

39484

AN:

151906

Hom.:

6925

Cov.:

show subpopulations

Gnomad AFR

AF:

0.475

Gnomad AMI

AF:

0.211

Gnomad AMR

AF:

0.318

Gnomad ASJ

AF:

0.0994

Gnomad EAS

AF:

0.412

Gnomad SAS

AF:

0.270

Gnomad FIN

AF:

0.0742

Gnomad MID

AF:

0.193

Gnomad NFE

AF:

0.143

Gnomad OTH

AF:

0.237

GnomAD2 exomes

AF:

0.227

AC:

56989

AN:

251200

AF XY:

0.214

show subpopulations

Gnomad AFR exome

AF:

0.477

Gnomad AMR exome

AF:

0.405

Gnomad ASJ exome

AF:

0.101

Gnomad EAS exome

AF:

0.397

Gnomad FIN exome

AF:

0.0744

Gnomad NFE exome

AF:

0.140

Gnomad OTH exome

AF:

0.189

GnomAD4 exome

AF:

0.177

AC:

259400

AN:

1461712

Hom.:

28817

Cov.:

AF XY:

0.177

AC XY:

128611

AN XY:

727160

show subpopulations

African (AFR)

AF:

0.488

AC:

16340

AN:

33470

American (AMR)

AF:

0.395

AC:

17665

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.106

AC:

2762

AN:

26136

East Asian (EAS)

AF:

0.435

AC:

17255

AN:

39690

South Asian (SAS)

AF:

0.265

AC:

22828

AN:

86246

European-Finnish (FIN)

AF:

0.0813

AC:

4342

AN:

53412

Middle Eastern (MID)

AF:

0.188

AC:

1070

AN:

5706

European-Non Finnish (NFE)

AF:

0.149

AC:

165332

AN:

1111948

Other (OTH)

AF:

0.196

AC:

11806

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

12204

24407

36611

48814

61018

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6490

12980

19470

25960

32450

<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:

0.260

AC:

39558

AN:

152024

Hom.:

6952

Cov.:

AF XY:

0.261

AC XY:

19376

AN XY:

74328

show subpopulations

African (AFR)

AF:

0.475

AC:

19673

AN:

41408

American (AMR)

AF:

0.318

AC:

4854

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.0994

AC:

345

AN:

3472

East Asian (EAS)

AF:

0.412

AC:

2121

AN:

5154

South Asian (SAS)

AF:

0.269

AC:

1296

AN:

4814

European-Finnish (FIN)

AF:

0.0742

AC:

787

AN:

10608

Middle Eastern (MID)

AF:

0.211

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.143

AC:

9727

AN:

67984

Other (OTH)

AF:

0.237

AC:

501

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1330

2660

3989

5319

6649

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

374

748

1122

1496

1870

<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:

0.170

Hom.:

968

Bravo

AF:

0.291

Asia WGS

AF:

0.383

AC:

1327

AN:

3478

EpiCase

AF:

0.139

EpiControl

AF:

0.141

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Spondyloepimetaphyseal dysplasia-short limb-abnormal calcification syndrome (2)

not specified (1)

Squamous cell lung carcinoma (1)

Warburg-cinotti syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.38

CADD

Benign

6.1

(source)

DANN

Benign

0.76

PhyloP100

0.24

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over