chr1-162755248-C-T

Position:

chr1-162755248-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2

The NM_006182.4(DDR2):c.510C>T(p.Thr170Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000699 in 1,613,996 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0038 ( 3 hom., cov: 32)

Exomes 𝑓: 0.00038 ( 6 hom. )

Consequence

DDR2
NM_006182.4 synonymous

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:2

Conservation

PhyloP100: -3.33

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BP6

Variant 1-162755248-C-T is Benign according to our data. Variant chr1-162755248-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 259934.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Benign=1}.

BP7

Synonymous conserved (PhyloP=-3.33 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00376 (572/152220) while in subpopulation AFR AF= 0.0124 (515/41540). AF 95% confidence interval is 0.0115. There are 3 homozygotes in gnomad4. There are 262 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 572 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DDR2	NM_006182.4 linkuse as main transcript	c.510C>T	p.Thr170Thr	synonymous_variant	6/18	ENST00000367921.8	NP_006173.2	Q16832A0A024R906

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DDR2	ENST00000367921.8 linkuse as main transcript	c.510C>T	p.Thr170Thr	synonymous_variant	6/18	1	NM_006182.4	ENSP00000356898.3	Q16832
DDR2	ENST00000367922.7 linkuse as main transcript	c.510C>T	p.Thr170Thr	synonymous_variant	7/19	1		ENSP00000356899.2	Q16832
DDR2	ENST00000446985.6 linkuse as main transcript	c.510C>T	p.Thr170Thr	synonymous_variant	6/18	3		ENSP00000400309.2	Q16832
DDR2	ENST00000672207.1 linkuse as main transcript	n.896C>T		non_coding_transcript_exon_variant	6/13

Frequencies

GnomAD3 genomes

AF:

0.00377

AC:

573

AN:

152102

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0124

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00282

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.000859

AC:

216

AN:

251346

Hom.:

AF XY:

0.000633

AC XY:

AN XY:

135830

show subpopulations

Gnomad AFR exome

AF:

0.0121

Gnomad AMR exome

AF:

0.000260

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000528

Gnomad OTH exome

AF:

0.000652

GnomAD4 exome

AF:

0.000380

AC:

556

AN:

1461776

Hom.:

Cov.:

AF XY:

0.000330

AC XY:

240

AN XY:

727198

show subpopulations

Gnomad4 AFR exome

AF:

0.0127

Gnomad4 AMR exome

AF:

0.000425

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000504

Gnomad4 OTH exome

AF:

0.000778

GnomAD4 genome

AF:

0.00376

AC:

572

AN:

152220

Hom.:

Cov.:

AF XY:

0.00352

AC XY:

262

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.0124

Gnomad4 AMR

AF:

0.00281

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00180

Hom.:

Bravo

AF:

0.00424

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Spondyloepimetaphyseal dysplasia-short limb-abnormal calcification syndrome

Uncertain:1

Uncertain significance, 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 30, 2024

- -

DDR2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 16, 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

BayesDel_noAF

Benign

-0.57

CADD

Benign

7.7

DANN

Benign

0.63

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