rs10494373

Variant names:

• chr1-162649572-A-C
• rs10494373
• NM_006182.4:c.-191-5639A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006182.4(DDR2):​c.-191-5639A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0745 in 152,232 control chromosomes in the GnomAD database, including 435 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 0.075 (435 hom., cov: 32)
• Consequence: DDR2 NM_006182.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.239
• Publications: 10 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: ClinGen, Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), Orphanet
• warburg-cinotti syndrome

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0889 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDR2	NM_006182.4	MANE Select	c.-191-5639A>C		intron	N/A	NP_006173.2	Q16832
	DDR2	NM_001014796.3		c.-271-5639A>C		intron	N/A	NP_001014796.1	Q16832
	DDR2	NM_001354982.2		c.-191-5639A>C		intron	N/A	NP_001341911.1	Q16832

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDR2	ENST00000367921.8	TSL:1 MANE Select	c.-191-5639A>C		intron	N/A	ENSP00000356898.3	Q16832
	DDR2	ENST00000367922.7	TSL:1	c.-271-5639A>C		intron	N/A	ENSP00000356899.2	Q16832
	DDR2	ENST00000877159.1		c.-191-5639A>C		intron	N/A	ENSP00000547218.1

Frequencies

GnomAD3 genomes AF: 0.0745 AC: 11329 AN: 152114 Hom.: 435 Cov.: 32

Gnomad AFR AF: 0.0691

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.0929

Gnomad ASJ AF: 0.0600

Gnomad EAS AF: 0.0156

Gnomad SAS AF: 0.0388

Gnomad FIN AF: 0.0968

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0771

Gnomad OTH AF: 0.0821

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

GnomAD4 genome AF: 0.0745 AC: 11343 AN: 152232 Hom.: 435 Cov.: 32 AF XY: 0.0739 AC XY: 5502 AN XY: 74420

African (AFR) AF: 0.0692 AC: 2876 AN: 41556

American (AMR) AF: 0.0929 AC: 1420 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0600 AC: 208 AN: 3468

East Asian (EAS) AF: 0.0156 AC: 81 AN: 5186

South Asian (SAS) AF: 0.0392 AC: 189 AN: 4820

European-Finnish (FIN) AF: 0.0968 AC: 1026 AN: 10598

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0770 AC: 5238 AN: 67996

Other (OTH) AF: 0.0818 AC: 173 AN: 2116

Alfa AF: 0.0767 Hom.: 763

Bravo AF: 0.0752

Asia WGS AF: 0.0240 AC: 83 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.4
DANN	Benign	0.83
PhyloP100		0.24
Mutation Taster		=99/1	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: rs10494373; hg19: chr1-162619362;