1-162679681-C-T

Variant names:

• chr1-162679681-C-T
• rs7521233
• NM_006182.4:c.-28+24307C>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.-28+24307C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.696 in 152,058 control chromosomes in the GnomAD database, including 37,908 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 (37908 hom., cov: 31)
• Consequence: DDR2 NM_006182.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.22
• Publications: 2 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=-1.02).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.772 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.-28+24307C>T		intron	N/A	NP_006173.2	Q16832
	DDR2	NM_001014796.3		c.-108+24307C>T		intron	N/A	NP_001014796.1	Q16832
	DDR2	NM_001354982.2		c.-28+24307C>T		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.-28+24307C>T		intron	N/A	ENSP00000356898.3	Q16832
	DDR2	ENST00000367922.7	TSL:1	c.-108+24307C>T		intron	N/A	ENSP00000356899.2	Q16832
	DDR2	ENST00000877159.1		c.-28+24307C>T		intron	N/A	ENSP00000547218.1

Frequencies

GnomAD3 genomes AF: 0.696 AC: 105798 AN: 151940 Hom.: 37908 Cov.: 31

Gnomad AFR AF: 0.529

Gnomad AMI AF: 0.681

Gnomad AMR AF: 0.613

Gnomad ASJ AF: 0.874

Gnomad EAS AF: 0.742

Gnomad SAS AF: 0.767

Gnomad FIN AF: 0.829

Gnomad MID AF: 0.823

Gnomad NFE AF: 0.778

Gnomad OTH AF: 0.708

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

GnomAD4 genome AF: 0.696 AC: 105834 AN: 152058 Hom.: 37908 Cov.: 31 AF XY: 0.698 AC XY: 51890 AN XY: 74332

African (AFR) AF: 0.528 AC: 21887 AN: 41428

American (AMR) AF: 0.613 AC: 9352 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.874 AC: 3033 AN: 3472

East Asian (EAS) AF: 0.743 AC: 3834 AN: 5162

South Asian (SAS) AF: 0.767 AC: 3693 AN: 4814

European-Finnish (FIN) AF: 0.829 AC: 8782 AN: 10596

Middle Eastern (MID) AF: 0.816 AC: 240 AN: 294

European-Non Finnish (NFE) AF: 0.778 AC: 52891 AN: 67998

Other (OTH) AF: 0.710 AC: 1501 AN: 2114

Alfa AF: 0.732 Hom.: 4913

Bravo AF: 0.671

Asia WGS AF: 0.727 AC: 2531 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.76
DANN	Benign	0.40
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: rs7521233; hg19: chr1-162649471;