rs10917589

Variant names:

• chr1-162708544-C-T
• rs10917589
• NM_006182.4:c.-27-10493C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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 Gene-Disease associations (from GenCC):

• spondyloepimetaphyseal dysplasia-short limb-abnormal calcification syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae), G2P, Orphanet
• warburg-cinotti syndrome

  Inheritance: Unknown, AD Classification: STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, G2P, Illumina, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006182.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDR2	NM_006182.4	MANE Select	c.-27-10493C>T		intron	N/A	NP_006173.2
	DDR2	NM_001014796.3		c.-28+3413C>T		intron	N/A	NP_001014796.1
	DDR2	NM_001354982.2		c.-27-10493C>T		intron	N/A	NP_001341911.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDR2	ENST00000367921.8	TSL:1 MANE Select	c.-27-10493C>T		intron	N/A	ENSP00000356898.3
	DDR2	ENST00000367922.7	TSL:1	c.-28+3413C>T		intron	N/A	ENSP00000356899.2
	DDR2	ENST00000446985.6	TSL:3	c.-27-10493C>T		intron	N/A	ENSP00000400309.2

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

African (AFR) AF: 0.249 AC: 10311 AN: 41438

American (AMR) AF: 0.226 AC: 3458 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0346 AC: 120 AN: 3472

East Asian (EAS) AF: 0.224 AC: 1158 AN: 5172

South Asian (SAS) AF: 0.100 AC: 484 AN: 4818

European-Finnish (FIN) AF: 0.0170 AC: 180 AN: 10606

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0673 AC: 4576 AN: 68020

Other (OTH) AF: 0.136 AC: 287 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.7
DANN	Benign	0.33
PhyloP100		-0.11
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10917589; hg19: chr1-162678334;