1-162770390-C-T

Position:

chr1-162770390-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 1P and 20B. PP2BP4_StrongBP6_Very_StrongBS1BS2

The NM_006182.4(DDR2):c.1382C>T(p.Ser461Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000427 in 1,614,136 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0024 ( 4 hom., cov: 32)

Exomes 𝑓: 0.00022 ( 1 hom. )

Consequence

DDR2
NM_006182.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 3.72

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.

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), DDR2. . Gene score misZ 2.2869 (greater than the threshold 3.09). Trascript score misZ 3.8204 (greater than threshold 3.09). GenCC has associacion of gene with warburg-cinotti syndrome, spondyloepimetaphyseal dysplasia-short limb-abnormal calcification syndrome.

BP4

Computational evidence support a benign effect (MetaRNN=0.006246835).

BP6

Variant 1-162770390-C-T is Benign according to our data. Variant chr1-162770390-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 286557.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00244 (372/152250) while in subpopulation AFR AF= 0.00862 (358/41542). AF 95% confidence interval is 0.00788. There are 4 homozygotes in gnomad4. There are 185 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 372 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DDR2	NM_006182.4 linkuse as main transcript	c.1382C>T	p.Ser461Leu	missense_variant	12/18	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.1382C>T	p.Ser461Leu	missense_variant	12/18	1	NM_006182.4	ENSP00000356898.3		Q16832

Frequencies

GnomAD3 genomes

AF:

0.00245

AC:

372

AN:

152132

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00864

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000720

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.000557

AC:

140

AN:

251358

Hom.:

AF XY:

0.000420

AC XY:

AN XY:

135838

show subpopulations

Gnomad AFR exome

AF:

0.00775

Gnomad AMR exome

AF:

0.000260

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.000652

GnomAD4 exome

AF:

0.000217

AC:

317

AN:

1461886

Hom.:

Cov.:

AF XY:

0.000183

AC XY:

133

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.00800

Gnomad4 AMR exome

AF:

0.000246

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000540

Gnomad4 OTH exome

AF:

0.000513

GnomAD4 genome

AF:

0.00244

AC:

372

AN:

152250

Hom.:

Cov.:

AF XY:

0.00249

AC XY:

185

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.00862

Gnomad4 AMR

AF:

0.000719

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000325

Hom.:

Bravo

AF:

0.00279

ESP6500AA

AF:

0.00862

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000733

AC:

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Apr 28, 2017	- -
Likely benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	May 04, 2023	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 25, 2024	- -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Mar 04, 2016

- -

DDR2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 10, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.22

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.22

T;T;T;.

Eigen

Benign

-0.17

Eigen_PC

Benign

0.079

FATHMM_MKL

Uncertain

0.85

LIST_S2

Uncertain

0.90

.;.;D;D

M_CAP

Benign

0.019

MetaRNN

Benign

0.0062

T;T;T;T

MetaSVM

Benign

-0.77

MutationAssessor

Benign

2.0

M;M;M;.

PrimateAI

Uncertain

0.51

PROVEAN

Benign

0.20

.;N;N;N

REVEL

Benign

0.13

Sift

Benign

0.68

.;T;T;T

Sift4G

Benign

0.34

.;T;T;T

Polyphen

0.0010

B;B;B;.

Vest4

0.47, 0.48

MVP

0.78

MPC

0.39

ClinPred

0.015

GERP RS

5.8

Varity_R

0.066

gMVP

0.32

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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