rs7553831

Variant names:

• chr1-162691221-T-G
• rs7553831
• NM_006182.4:c.-27-27816T>G

Variant summary

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

The ENST00000367921.8(DDR2):​c.-27-27816T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.698 in 151,984 control chromosomes in the GnomAD database, including 38,189 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 0.70 (38189 hom., cov: 31)
• Consequence: DDR2 ENST00000367921.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.25
• Publications: 6 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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.778 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000367921.8. 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.-27-27816T>G		intron	N/A	NP_006173.2
	DDR2	NM_001014796.3		c.-107-13831T>G		intron	N/A	NP_001014796.1
	DDR2	NM_001354982.2		c.-27-27816T>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.-27-27816T>G		intron	N/A	ENSP00000356898.3
	DDR2	ENST00000367922.7	TSL:1	c.-107-13831T>G		intron	N/A	ENSP00000356899.2
	DDR2	ENST00000446985.6	TSL:3	c.-27-27816T>G		intron	N/A	ENSP00000400309.2

Frequencies

GnomAD3 genomes AF: 0.698 AC: 106013 AN: 151868 Hom.: 38174 Cov.: 31

Gnomad AFR AF: 0.521

Gnomad AMI AF: 0.765

Gnomad AMR AF: 0.613

Gnomad ASJ AF: 0.890

Gnomad EAS AF: 0.742

Gnomad SAS AF: 0.765

Gnomad FIN AF: 0.830

Gnomad MID AF: 0.813

Gnomad NFE AF: 0.784

Gnomad OTH AF: 0.715

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

GnomAD4 genome AF: 0.698 AC: 106073 AN: 151984 Hom.: 38189 Cov.: 31 AF XY: 0.700 AC XY: 51994 AN XY: 74272

African (AFR) AF: 0.522 AC: 21604 AN: 41418

American (AMR) AF: 0.613 AC: 9350 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.890 AC: 3089 AN: 3472

East Asian (EAS) AF: 0.742 AC: 3821 AN: 5148

South Asian (SAS) AF: 0.765 AC: 3683 AN: 4812

European-Finnish (FIN) AF: 0.830 AC: 8786 AN: 10584

Middle Eastern (MID) AF: 0.806 AC: 237 AN: 294

European-Non Finnish (NFE) AF: 0.784 AC: 53291 AN: 67976

Other (OTH) AF: 0.717 AC: 1514 AN: 2112

Alfa AF: 0.753 Hom.: 135996

Bravo AF: 0.672

Asia WGS AF: 0.729 AC: 2538 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	10
DANN	Benign	0.73
PhyloP100		1.3
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: rs7553831; hg19: chr1-162661011;