chr6-30897427-A-C

Variant names:

• chr6-30897427-A-C
• rs2267641
• NM_001297654.2:c.2046A>C

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP7 BA1

The NM_001297654.2(DDR1):​c.2046A>C​(p.Pro682Pro) 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. 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
• Publications: 30 publications found

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]

DDR1 Gene-Disease associations (from GenCC):

• chondrodysplasia

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001297654.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDR1	NM_001297654.2	MANE Select	c.2046A>C	p.Pro682Pro	synonymous	Exon 15 of 18	NP_001284583.1
	DDR1	NM_001387892.1		c.2064A>C	p.Pro688Pro	synonymous	Exon 15 of 18	NP_001374821.1
	DDR1	NM_013994.3		c.2064A>C	p.Pro688Pro	synonymous	Exon 15 of 18	NP_054700.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDR1	ENST00000376568.8	TSL:1 MANE Select	c.2046A>C	p.Pro682Pro	synonymous	Exon 15 of 18	ENSP00000365752.3
	DDR1	ENST00000452441.5	TSL:1	c.2046A>C	p.Pro682Pro	synonymous	Exon 16 of 19	ENSP00000405039.1
	DDR1	ENST00000376567.6	TSL:1	c.1935A>C	p.Pro645Pro	synonymous	Exon 13 of 16	ENSP00000365751.2

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

GnomAD2 exomes AF: 0.239 AC: 60012 AN: 251390 AF XY: 0.240

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 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

African (AFR) AF: 0.126 AC: 4222 AN: 33478

American (AMR) AF: 0.386 AC: 17250 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.211 AC: 5515 AN: 26134

East Asian (EAS) AF: 0.411 AC: 16323 AN: 39698

South Asian (SAS) AF: 0.379 AC: 32676 AN: 86256

European-Finnish (FIN) AF: 0.224 AC: 11946 AN: 53398

Middle Eastern (MID) AF: 0.186 AC: 1071 AN: 5764

European-Non Finnish (NFE) AF: 0.150 AC: 166688 AN: 1111968

Other (OTH) AF: 0.208 AC: 12577 AN: 60394

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

African (AFR) AF: 0.132 AC: 5492 AN: 41508

American (AMR) AF: 0.300 AC: 4584 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.203 AC: 702 AN: 3464

East Asian (EAS) AF: 0.373 AC: 1916 AN: 5142

South Asian (SAS) AF: 0.400 AC: 1919 AN: 4796

European-Finnish (FIN) AF: 0.223 AC: 2367 AN: 10594

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.156 AC: 10615 AN: 67994

Other (OTH) AF: 0.189 AC: 399 AN: 2108

Alfa AF: 0.158 Hom.: 1172

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	5.2
DANN	Benign	0.59
PhyloP100		-1.8
PromoterAI		-0.0034	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=90/10	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: rs2267641; hg19: chr6-30865204; COSMIC: COSV61318609; COSMIC: COSV61318609;