rs10494373

Variant names:

• chr1-162649572-A-C
• rs10494373
• NM_006182.4:c.-191-5639A>C

Variant summary

Our verdict is Benign. The variant received -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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
DDR2	NM_006182.4	c.-191-5639A>C		intron_variant	Intron 1 of 17	ENST00000367921.8	NP_006173.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDR2	ENST00000367921.8	c.-191-5639A>C		intron_variant	Intron 1 of 17	1	NM_006182.4	ENSP00000356898.3

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 AC: 0.0692078 AN: 0.0692078

Gnomad4 AMR AF: 0.0929 AC: 0.0928955 AN: 0.0928955

Gnomad4 ASJ AF: 0.0600 AC: 0.0599769 AN: 0.0599769

Gnomad4 EAS AF: 0.0156 AC: 0.015619 AN: 0.015619

Gnomad4 SAS AF: 0.0392 AC: 0.0392116 AN: 0.0392116

Gnomad4 FIN AF: 0.0968 AC: 0.0968107 AN: 0.0968107

Gnomad4 NFE AF: 0.0770 AC: 0.0770339 AN: 0.0770339

Gnomad4 OTH AF: 0.0818 AC: 0.081758 AN: 0.081758

Alfa AF: 0.0767 Hom.: 763

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
Mutation Taster		=99/1	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

Publications

LitVar

Other links and lift over

dbSNP: rs10494373; hg19: chr1-162619362;