rs10494373

chr1-162649572-A-C

Variant summary

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

The NM_006182.4(DDR2):c.-191-5639A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0745 in 152,232 control chromosomes in the GnomAD database, including 435 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 0.075 (435 hom., cov: 32)
• Consequence: DDR2 NM_006182.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.239

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0889 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DDR2	NM_006182.4	c.-191-5639A>C		intron_variant		ENST00000367921.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DDR2	ENST00000367921.8	c.-191-5639A>C		intron_variant		1	NM_006182.4	P1

Frequencies

GnomAD3 genomes AF: 0.0745 AC: 11329 AN: 152114 Hom.: 435 Cov.: 32

Gnomad AFR AF: 0.0691

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.0929

Gnomad ASJ AF: 0.0600

Gnomad EAS AF: 0.0156

Gnomad SAS AF: 0.0388

Gnomad FIN AF: 0.0968

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0771

Gnomad OTH AF: 0.0821

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

GnomAD4 genome AF: 0.0745 AC: 11343 AN: 152232 Hom.: 435 Cov.: 32 AF XY: 0.0739 AC XY: 5502 AN XY: 74420

Gnomad4 AFR AF: 0.0692

Gnomad4 AMR AF: 0.0929

Gnomad4 ASJ AF: 0.0600

Gnomad4 EAS AF: 0.0156

Gnomad4 SAS AF: 0.0392

Gnomad4 FIN AF: 0.0968

Gnomad4 NFE AF: 0.0770

Gnomad4 OTH AF: 0.0818

Alfa AF: 0.0763 Hom.: 602

Bravo AF: 0.0752

Asia WGS AF: 0.0240 AC: 83 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	5.4
Dann	Benign	0.83

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: rs10494373; hg19: chr1-162619362;