chr1-162770537-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_006182.4(DDR2):c.1504+25T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.991 in 1,611,812 control chromosomes in the GnomAD database, including 793,088 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.96 ( 69714 hom., cov: 29)

Exomes 𝑓: 1.0 ( 723374 hom. )

Consequence

DDR2
NM_006182.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts U:1B:5

Conservation

PhyloP100: -1.39

Publications

10 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 -16 ACMG points.

BP6

Variant 1-162770537-T-C is Benign according to our data. Variant chr1-162770537-T-C is described in ClinVar as Benign. ClinVar VariationId is 259930.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 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	Effect	Exon Rank	Protein
DDR2	NM_006182.4	MANE Select	c.1504+25T>C	intron	N/A	NP_006173.2
DDR2	NM_001014796.3		c.1504+25T>C	intron	N/A	NP_001014796.1
DDR2	NM_001354982.2		c.1504+25T>C	intron	N/A	NP_001341911.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
DDR2	ENST00000367921.8	TSL:1 MANE Select	c.1504+25T>C	intron	N/A	ENSP00000356898.3
DDR2	ENST00000367922.7	TSL:1	c.1504+25T>C	intron	N/A	ENSP00000356899.2
DDR2	ENST00000458105.1	TSL:2	n.359T>C	non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes

AF:

0.955

AC:

145112

AN:

151904

Hom.:

69673

Cov.:

show subpopulations

Gnomad AFR

AF:

0.845

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.984

Gnomad ASJ

AF:

1.00

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

0.998

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

0.994

Gnomad NFE

AF:

0.999

Gnomad OTH

AF:

0.964

GnomAD2 exomes

AF:

0.988

AC:

247517

AN:

250514

AF XY:

0.991

show subpopulations

Gnomad AFR exome

AF:

0.842

Gnomad AMR exome

AF:

0.992

Gnomad ASJ exome

AF:

1.00

Gnomad EAS exome

AF:

1.00

Gnomad FIN exome

AF:

1.00

Gnomad NFE exome

AF:

0.999

Gnomad OTH exome

AF:

0.992

GnomAD4 exome

AF:

0.995

AC:

1452822

AN:

1459790

Hom.:

723374

Cov.:

AF XY:

0.996

AC XY:

723311

AN XY:

726314

show subpopulations

African (AFR)

AF:

0.840

AC:

28078

AN:

33416

American (AMR)

AF:

0.990

AC:

44254

AN:

44688

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

26126

AN:

26126

East Asian (EAS)

AF:

1.00

AC:

39643

AN:

39644

South Asian (SAS)

AF:

0.999

AC:

86158

AN:

86208

European-Finnish (FIN)

AF:

1.00

AC:

53392

AN:

53394

Middle Eastern (MID)

AF:

0.989

AC:

5700

AN:

5762

European-Non Finnish (NFE)

AF:

1.00

AC:

1109844

AN:

1110224

Other (OTH)

AF:

0.988

AC:

59627

AN:

60328

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

363

727

1090

1454

1817

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21614

43228

64842

86456

108070

<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:

0.955

AC:

145213

AN:

152022

Hom.:

69714

Cov.:

AF XY:

0.956

AC XY:

71048

AN XY:

74284

show subpopulations

African (AFR)

AF:

0.845

AC:

34982

AN:

41416

American (AMR)

AF:

0.984

AC:

15023

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

3472

AN:

3472

East Asian (EAS)

AF:

1.00

AC:

5132

AN:

5134

South Asian (SAS)

AF:

0.999

AC:

4792

AN:

4796

European-Finnish (FIN)

AF:

1.00

AC:

10604

AN:

10604

Middle Eastern (MID)

AF:

0.993

AC:

292

AN:

294

European-Non Finnish (NFE)

AF:

0.999

AC:

67972

AN:

68012

Other (OTH)

AF:

0.964

AC:

2034

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

295

590

885

1180

1475

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

908

1816

2724

3632

4540

<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:

0.982

Hom.:

201867

Bravo

AF:

0.950

TwinsUK

AF:

1.00

AC:

3707

ALSPAC

AF:

1.00

AC:

3854

ESP6500AA

AF:

0.847

AC:

3731

ESP6500EA

AF:

0.999

AC:

8593

ExAC

AF:

0.985

AC:

119584

Asia WGS

AF:

0.992

AC:

3449

AN:

3478

EpiCase

AF:

1.00

EpiControl

AF:

0.999

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (1)

Spondyloepimetaphyseal dysplasia-short limb-abnormal calcification syndrome (1)

Squamous cell lung carcinoma (1)

Warburg-cinotti syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.76

BayesDel_noAF

Benign

-0.72

CADD

Benign

4.6

(source)

DANN

Benign

0.55

Eigen

Benign

-1.9

Eigen_PC

Benign

-2.2

FATHMM_MKL

Benign

0.019

LIST_S2

Benign

0.15

MetaRNN

Benign

0.0000011

MetaSVM

Benign

-1.1

PhyloP100

-1.4

PROVEAN

Benign

0.31

REVEL

Benign

0.0060

Sift

Pathogenic

0.0

Sift4G

Benign

1.0

ClinPred

0.016

GERP RS

-10

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.24

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.24

Position offset: 29

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over