rs2298258

Positions:

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_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. In-silico tool predicts a benign outcome for this variant. 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

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 links:

DDR2 (HGNC:):

DDR2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.38).

BP6

Variant 1-162767326-C-G is Benign according to our data. Variant chr1-162767326-C-G is described in ClinVar as [Benign]. Clinvar id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DDR2	NM_006182.4 linkuse as main transcript	c.1260C>G	p.Leu420Leu	synonymous_variant	11/18	ENST00000367921.8	NP_006173.2	Q16832A0A024R906

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DDR2	ENST00000367921.8 linkuse as main transcript	c.1260C>G	p.Leu420Leu	synonymous_variant	11/18	1	NM_006182.4	ENSP00000356898.3		Q16832

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

GnomAD3 exomes

AF:

0.227

AC:

56989

AN:

251200

Hom.:

8770

AF XY:

0.214

AC XY:

29030

AN XY:

135758

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 SAS exome

AF:

0.268

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

Gnomad4 AFR exome

AF:

0.488

Gnomad4 AMR exome

AF:

0.395

Gnomad4 ASJ exome

AF:

0.106

Gnomad4 EAS exome

AF:

0.435

Gnomad4 SAS exome

AF:

0.265

Gnomad4 FIN exome

AF:

0.0813

Gnomad4 NFE exome

AF:

0.149

Gnomad4 OTH exome

AF:

0.196

GnomAD4 genome

AF:

0.260

AC:

39558

AN:

152024

Hom.:

6952

Cov.:

AF XY:

0.261

AC XY:

19376

AN XY:

74328

show subpopulations

Gnomad4 AFR

AF:

0.475

Gnomad4 AMR

AF:

0.318

Gnomad4 ASJ

AF:

0.0994

Gnomad4 EAS

AF:

0.412

Gnomad4 SAS

AF:

0.269

Gnomad4 FIN

AF:

0.0742

Gnomad4 NFE

AF:

0.143

Gnomad4 OTH

AF:

0.237

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

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 20, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

Spondyloepimetaphyseal dysplasia-short limb-abnormal calcification syndrome

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 30, 2021	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Warburg-cinotti syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

Squamous cell lung carcinoma

Benign:1

Likely benign, no assertion criteria provided

clinical testing;in vivo

Faculté Pluridciplinaire Nador, Université Mohamed Premier

May 05, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.38

CADD

Benign

6.1

DANN

Benign

0.76

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

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