rs10917589

chr1-162708544-C-T

Variant summary

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

The NM_006182.4(DDR2):c.-27-10493C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 152,124 control chromosomes in the GnomAD database, including 2,099 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 0.14 (2099 hom., cov: 32)
• Consequence: DDR2 NM_006182.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.114

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.245 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DDR2	NM_006182.4	c.-27-10493C>T		intron_variant		ENST00000367921.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DDR2	ENST00000367921.8	c.-27-10493C>T		intron_variant		1	NM_006182.4	P1

Frequencies

GnomAD3 genomes AF: 0.136 AC: 20683 AN: 152006 Hom.: 2099 Cov.: 32

Gnomad AFR AF: 0.249

Gnomad AMI AF: 0.118

Gnomad AMR AF: 0.226

Gnomad ASJ AF: 0.0346

Gnomad EAS AF: 0.224

Gnomad SAS AF: 0.102

Gnomad FIN AF: 0.0170

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0673

Gnomad OTH AF: 0.136

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

GnomAD4 genome AF: 0.136 AC: 20709 AN: 152124 Hom.: 2099 Cov.: 32 AF XY: 0.137 AC XY: 10221 AN XY: 74380

Gnomad4 AFR AF: 0.249

Gnomad4 AMR AF: 0.226

Gnomad4 ASJ AF: 0.0346

Gnomad4 EAS AF: 0.224

Gnomad4 SAS AF: 0.100

Gnomad4 FIN AF: 0.0170

Gnomad4 NFE AF: 0.0673

Gnomad4 OTH AF: 0.136

Alfa AF: 0.119 Hom.: 268

Bravo AF: 0.159

Asia WGS AF: 0.171 AC: 592 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	3.7
Dann	Benign	0.33

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: rs10917589; hg19: chr1-162678334;