1-162770537-T-C

Variant names:

Variant summary

Our verdict is Benign. Variant got -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

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 259930.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-162770537-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDR2	NM_006182.4 link	c.1504+25T>C		intron_variant	Intron 12 of 17	ENST00000367921.8	NP_006173.2	Q16832A0A024R906

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDR2	ENST00000367921.8 link	c.1504+25T>C		intron_variant	Intron 12 of 17	1	NM_006182.4	ENSP00000356898.3		Q16832

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

GnomAD3 exomes

AF:

0.988

AC:

247517

AN:

250514

Hom.:

122466

AF XY:

0.991

AC XY:

134227

AN XY:

135424

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 SAS exome

AF:

0.999

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

Gnomad4 AFR exome

AF:

0.840

Gnomad4 AMR exome

AF:

0.990

Gnomad4 ASJ exome

AF:

1.00

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

0.999

Gnomad4 FIN exome

AF:

1.00

Gnomad4 NFE exome

AF:

1.00

Gnomad4 OTH exome

AF:

0.988

GnomAD4 genome

AF:

0.955

AC:

145213

AN:

152022

Hom.:

69714

Cov.:

AF XY:

0.956

AC XY:

71048

AN XY:

74284

show subpopulations

Gnomad4 AFR

AF:

0.845

Gnomad4 AMR

AF:

0.984

Gnomad4 ASJ

AF:

1.00

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

0.999

Gnomad4 FIN

AF:

1.00

Gnomad4 NFE

AF:

0.999

Gnomad4 OTH

AF:

0.964

Alfa

AF:

0.992

Hom.:

131042

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

Significance: Benign

Submissions summary: Uncertain:1Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Oct 16, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Squamous cell lung carcinoma

Uncertain:1

May 05, 2020

Faculté Pluridciplinaire Nador, Université Mohamed Premier

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: clinical testing;in vivo

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Warburg-cinotti syndrome

Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Spondyloepimetaphyseal dysplasia-short limb-abnormal calcification syndrome

Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.76

BayesDel_noAF

Benign

-0.72

CADD

Benign

4.6

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

PROVEAN

Benign

0.31

REVEL

Benign

0.0060

Sift

Pathogenic

0.0

Sift4G

Benign

1.0

ClinPred

0.016

GERP RS

-10

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

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