1-162721669-G-A

Variant names:

• chr1-162721669-G-A
• rs2806424
• NM_006182.4:c.82+2524G>A

Variant summary

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

The NM_006182.4(DDR2):​c.82+2524G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.583 in 152,074 control chromosomes in the GnomAD database, including 29,505 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 0.58 (29505 hom., cov: 32)
• Consequence: DDR2 NM_006182.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.154
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.735 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDR2	NM_006182.4	c.82+2524G>A		intron_variant	Intron 3 of 17	ENST00000367921.8	NP_006173.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDR2	ENST00000367921.8	c.82+2524G>A		intron_variant	Intron 3 of 17	1	NM_006182.4	ENSP00000356898.3

Frequencies

GnomAD3 genomes AF: 0.583 AC: 88647 AN: 151958 Hom.: 29506 Cov.: 32

Gnomad AFR AF: 0.248

Gnomad AMI AF: 0.713

Gnomad AMR AF: 0.557

Gnomad ASJ AF: 0.824

Gnomad EAS AF: 0.570

Gnomad SAS AF: 0.672

Gnomad FIN AF: 0.792

Gnomad MID AF: 0.744

Gnomad NFE AF: 0.740

Gnomad OTH AF: 0.610

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

GnomAD4 genome AF: 0.583 AC: 88652 AN: 152074 Hom.: 29505 Cov.: 32 AF XY: 0.586 AC XY: 43541 AN XY: 74344

African (AFR) AF: 0.247 AC: 10258 AN: 41484

American (AMR) AF: 0.557 AC: 8506 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.824 AC: 2860 AN: 3470

East Asian (EAS) AF: 0.570 AC: 2940 AN: 5160

South Asian (SAS) AF: 0.672 AC: 3246 AN: 4828

European-Finnish (FIN) AF: 0.792 AC: 8375 AN: 10580

Middle Eastern (MID) AF: 0.738 AC: 217 AN: 294

European-Non Finnish (NFE) AF: 0.740 AC: 50313 AN: 67970

Other (OTH) AF: 0.611 AC: 1287 AN: 2106

Alfa AF: 0.639 Hom.: 12718

Bravo AF: 0.549

Asia WGS AF: 0.547 AC: 1908 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.5
DANN	Benign	0.58
PhyloP100		-0.15
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: rs2806424; hg19: chr1-162691459;