rs1264320

Variant names:

• chr6-30893223-C-T
• rs1264320
• NM_001297654.2:c.1196-49C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001297654.2(DDR1):​c.1196-49C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.333 in 1,592,636 control chromosomes in the GnomAD database, including 92,123 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 0.28 (6843 hom., cov: 33)
  • Exomes 𝑓: 0.34 (85280 hom.)
• Consequence: DDR1 NM_001297654.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.490
• Publications: 11 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.358 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDR1	NM_001297654.2	c.1196-49C>T		intron_variant	Intron 9 of 17	ENST00000376568.8	NP_001284583.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDR1	ENST00000376568.8	c.1196-49C>T		intron_variant	Intron 9 of 17	1	NM_001297654.2	ENSP00000365752.3

Frequencies

GnomAD3 genomes AF: 0.280 AC: 42582 AN: 152084 Hom.: 6845 Cov.: 33

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.308

Gnomad AMR AF: 0.242

Gnomad ASJ AF: 0.391

Gnomad EAS AF: 0.256

Gnomad SAS AF: 0.268

Gnomad FIN AF: 0.393

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.362

Gnomad OTH AF: 0.281

GnomAD2 exomes AF: 0.315 AC: 74164 AN: 235212 AF XY: 0.324

Gnomad AFR exome AF: 0.119

Gnomad AMR exome AF: 0.217

Gnomad ASJ exome AF: 0.375

Gnomad EAS exome AF: 0.285

Gnomad FIN exome AF: 0.399

Gnomad NFE exome AF: 0.371

Gnomad OTH exome AF: 0.336

GnomAD4 exome AF: 0.339 AC: 488467 AN: 1440434 Hom.: 85280 Cov.: 43 AF XY: 0.339 AC XY: 242475 AN XY: 715360

African (AFR) AF: 0.116 AC: 3853 AN: 33304

American (AMR) AF: 0.220 AC: 9637 AN: 43882

Ashkenazi Jewish (ASJ) AF: 0.365 AC: 9206 AN: 25190

East Asian (EAS) AF: 0.242 AC: 9548 AN: 39462

South Asian (SAS) AF: 0.280 AC: 23792 AN: 84822

European-Finnish (FIN) AF: 0.387 AC: 16964 AN: 43794

Middle Eastern (MID) AF: 0.330 AC: 1888 AN: 5714

European-Non Finnish (NFE) AF: 0.358 AC: 394967 AN: 1104450

Other (OTH) AF: 0.311 AC: 18612 AN: 59816

GnomAD4 genome AF: 0.280 AC: 42591 AN: 152202 Hom.: 6843 Cov.: 33 AF XY: 0.281 AC XY: 20911 AN XY: 74392

African (AFR) AF: 0.125 AC: 5193 AN: 41566

American (AMR) AF: 0.242 AC: 3706 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.391 AC: 1358 AN: 3470

East Asian (EAS) AF: 0.256 AC: 1324 AN: 5176

South Asian (SAS) AF: 0.267 AC: 1289 AN: 4826

European-Finnish (FIN) AF: 0.393 AC: 4158 AN: 10586

Middle Eastern (MID) AF: 0.378 AC: 111 AN: 294

European-Non Finnish (NFE) AF: 0.362 AC: 24584 AN: 67960

Other (OTH) AF: 0.279 AC: 588 AN: 2110

Alfa AF: 0.328 Hom.: 3930

Bravo AF: 0.263

Asia WGS AF: 0.214 AC: 748 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	3.4
DANN	Benign	0.86
PhyloP100		-0.49
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1264320; hg19: chr6-30861000; COSMIC: COSV61318543; COSMIC: COSV61318543;