chr1-162634091-A-G

Variant names:

• chr1-162634091-A-G
• rs6702820
• NM_006182.4:c.-192+1460A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.285 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.-192+1460A>G		intron	N/A	NP_006173.2
	DDR2	NM_001014796.3		c.-272+1460A>G		intron	N/A	NP_001014796.1
	DDR2	NM_001354982.2		c.-192+1998A>G		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.-192+1460A>G		intron	N/A	ENSP00000356898.3
	DDR2	ENST00000367922.7	TSL:1	c.-272+1460A>G		intron	N/A	ENSP00000356899.2
	DDR2	ENST00000446985.6	TSL:3	c.-192+2644A>G		intron	N/A	ENSP00000400309.2

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

African (AFR) AF: 0.0757 AC: 3144 AN: 41532

American (AMR) AF: 0.292 AC: 4470 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.207 AC: 718 AN: 3468

East Asian (EAS) AF: 0.216 AC: 1118 AN: 5166

South Asian (SAS) AF: 0.176 AC: 849 AN: 4814

European-Finnish (FIN) AF: 0.145 AC: 1535 AN: 10588

Middle Eastern (MID) AF: 0.178 AC: 52 AN: 292

European-Non Finnish (NFE) AF: 0.233 AC: 15846 AN: 67990

Other (OTH) AF: 0.212 AC: 447 AN: 2106

Alfa AF: 0.225 Hom.: 2267

Bravo AF: 0.196

Asia WGS AF: 0.202 AC: 701 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.11
DANN	Benign	0.43
PhyloP100		-1.2
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: rs6702820; hg19: chr1-162603881;