rs2267641

chr6-30897427-A-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001297654.2(DDR1):c.2046A>C(p.Pro682=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 1,613,914 control chromosomes in the GnomAD database, including 33,041 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 0.19 (3158 hom., cov: 32)
  • Exomes 𝑓: 0.18 (29883 hom.)
• Consequence: DDR1 NM_001297654.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.76

Genes affected

DDR1 (HGNC:2730): (discoidin domain receptor tyrosine kinase 1) Receptor tyrosine kinases play a key role in the communication of cells with their microenvironment. These kinases are involved in the regulation of cell growth, differentiation and metabolism. The protein encoded by this gene belongs to a subfamily of tyrosine kinase receptors with homology to Dictyostelium discoideum protein discoidin I in their extracellular domain, and that are activated by various types of collagen. Expression of this protein is restricted to epithelial cells, particularly in the kidney, lung, gastrointestinal tract, and brain. In addition, it has been shown to be significantly overexpressed in several human tumors. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Feb 2011]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP7: Synonymous conserved (PhyloP=-1.76 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.385 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DDR1	NM_001297654.2	c.2046A>C	p.Pro682=	synonymous_variant	15/18	ENST00000376568.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DDR1	ENST00000376568.8	c.2046A>C	p.Pro682=	synonymous_variant	15/18	1	NM_001297654.2	P1

Frequencies

GnomAD3 genomes AF: 0.186 AC: 28275 AN: 151982 Hom.: 3143 Cov.: 32

Gnomad AFR AF: 0.133

Gnomad AMI AF: 0.293

Gnomad AMR AF: 0.299

Gnomad ASJ AF: 0.203

Gnomad EAS AF: 0.372

Gnomad SAS AF: 0.401

Gnomad FIN AF: 0.223

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.156

Gnomad OTH AF: 0.181

GnomAD3 exomes AF: 0.239 AC: 60012 AN: 251390 Hom.: 8807 AF XY: 0.240 AC XY: 32604 AN XY: 135876

Gnomad AFR exome AF: 0.130

Gnomad AMR exome AF: 0.396

Gnomad ASJ exome AF: 0.207

Gnomad EAS exome AF: 0.340

Gnomad SAS exome AF: 0.384

Gnomad FIN exome AF: 0.222

Gnomad NFE exome AF: 0.159

Gnomad OTH exome AF: 0.208

GnomAD4 exome AF: 0.184 AC: 268268 AN: 1461814 Hom.: 29883 Cov.: 39 AF XY: 0.189 AC XY: 137115 AN XY: 727206

Gnomad4 AFR exome AF: 0.126

Gnomad4 AMR exome AF: 0.386

Gnomad4 ASJ exome AF: 0.211

Gnomad4 EAS exome AF: 0.411

Gnomad4 SAS exome AF: 0.379

Gnomad4 FIN exome AF: 0.224

Gnomad4 NFE exome AF: 0.150

Gnomad4 OTH exome AF: 0.208

GnomAD4 genome AF: 0.186 AC: 28308 AN: 152100 Hom.: 3158 Cov.: 32 AF XY: 0.196 AC XY: 14535 AN XY: 74344

Gnomad4 AFR AF: 0.132

Gnomad4 AMR AF: 0.300

Gnomad4 ASJ AF: 0.203

Gnomad4 EAS AF: 0.373

Gnomad4 SAS AF: 0.400

Gnomad4 FIN AF: 0.223

Gnomad4 NFE AF: 0.156

Gnomad4 OTH AF: 0.189

Alfa AF: 0.163 Hom.: 948

Bravo AF: 0.185

Asia WGS AF: 0.441 AC: 1530 AN: 3478

EpiCase AF: 0.155

EpiControl AF: 0.162

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
Cadd	Benign	5.2
Dann	Benign	0.59
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs2267641; hg19: chr6-30865204; COSMIC: COSV61318609; COSMIC: COSV61318609;