rs6702820

Positions:

• chr1-162634091-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006182.4(DDR2):​c.-192+1460A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 152,154 control chromosomes in the GnomAD database, including 3,202 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.19 (3202 hom., cov: 32)
• Consequence: DDR2 NM_006182.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.22

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.285 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DDR2	NM_006182.4	c.-192+1460A>G		intron_variant		ENST00000367921.8	NP_006173.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DDR2	ENST00000367921.8	c.-192+1460A>G		intron_variant		1	NM_006182.4	ENSP00000356898.3

Frequencies

GnomAD3 genomes AF: 0.187 AC: 28376 AN: 152038 Hom.: 3195 Cov.: 32

Gnomad AFR AF: 0.0758

Gnomad AMI AF: 0.227

Gnomad AMR AF: 0.292

Gnomad ASJ AF: 0.207

Gnomad EAS AF: 0.217

Gnomad SAS AF: 0.176

Gnomad FIN AF: 0.145

Gnomad MID AF: 0.188

Gnomad NFE AF: 0.233

Gnomad OTH AF: 0.212

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.187 AC: 28386 AN: 152154 Hom.: 3202 Cov.: 32 AF XY: 0.184 AC XY: 13669 AN XY: 74390

Gnomad4 AFR AF: 0.0757

Gnomad4 AMR AF: 0.292

Gnomad4 ASJ AF: 0.207

Gnomad4 EAS AF: 0.216

Gnomad4 SAS AF: 0.176

Gnomad4 FIN AF: 0.145

Gnomad4 NFE AF: 0.233

Gnomad4 OTH AF: 0.212

Alfa AF: 0.224 Hom.: 2047

Bravo AF: 0.196

Asia WGS AF: 0.202 AC: 701 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.11
DANN	Benign	0.43

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

Other links and lift over

dbSNP: rs6702820; hg19: chr1-162603881;