rs4038287

Positions:

• chr1-162723979-T-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006182.4(DDR2):​c.82+4834T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0421 in 152,312 control chromosomes in the GnomAD database, including 204 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 0.042 (204 hom., cov: 32)
• Consequence: DDR2 NM_006182.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.764

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DDR2	NM_006182.4	c.82+4834T>A		intron_variant		ENST00000367921.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DDR2	ENST00000367921.8	c.82+4834T>A		intron_variant		1	NM_006182.4	P1

Frequencies

GnomAD3 genomes AF: 0.0419 AC: 6372 AN: 152194 Hom.: 200 Cov.: 32

Gnomad AFR AF: 0.0638

Gnomad AMI AF: 0.0274

Gnomad AMR AF: 0.0416

Gnomad ASJ AF: 0.0161

Gnomad EAS AF: 0.147

Gnomad SAS AF: 0.0822

Gnomad FIN AF: 0.0176

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0233

Gnomad OTH AF: 0.0372

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

GnomAD4 genome AF: 0.0421 AC: 6409 AN: 152312 Hom.: 204 Cov.: 32 AF XY: 0.0423 AC XY: 3151 AN XY: 74484

Gnomad4 AFR AF: 0.0644

Gnomad4 AMR AF: 0.0418

Gnomad4 ASJ AF: 0.0161

Gnomad4 EAS AF: 0.147

Gnomad4 SAS AF: 0.0825

Gnomad4 FIN AF: 0.0176

Gnomad4 NFE AF: 0.0233

Gnomad4 OTH AF: 0.0373

Alfa AF: 0.0329 Hom.: 9

Bravo AF: 0.0454

Asia WGS AF: 0.123 AC: 426 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.54
DANN	Benign	0.84

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

Publications

LitVar

Other links and lift over

dbSNP: rs4038287; hg19: chr1-162693769;