rs1264320

chr6-30893223-C-T

Variant summary

Our verdict is Benign. Variant got -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

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 -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/exons	MANE	UniProt
DDR1	NM_001297654.2	c.1196-49C>T		intron_variant		ENST00000376568.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DDR1	ENST00000376568.8	c.1196-49C>T		intron_variant		1	NM_001297654.2	P1

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

GnomAD3 exomes AF: 0.315 AC: 74164 AN: 235212 Hom.: 12458 AF XY: 0.324 AC XY: 41371 AN XY: 127820

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 SAS exome AF: 0.280

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

Gnomad4 AFR exome AF: 0.116

Gnomad4 AMR exome AF: 0.220

Gnomad4 ASJ exome AF: 0.365

Gnomad4 EAS exome AF: 0.242

Gnomad4 SAS exome AF: 0.280

Gnomad4 FIN exome AF: 0.387

Gnomad4 NFE exome AF: 0.358

Gnomad4 OTH exome AF: 0.311

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

Gnomad4 AFR AF: 0.125

Gnomad4 AMR AF: 0.242

Gnomad4 ASJ AF: 0.391

Gnomad4 EAS AF: 0.256

Gnomad4 SAS AF: 0.267

Gnomad4 FIN AF: 0.393

Gnomad4 NFE AF: 0.362

Gnomad4 OTH AF: 0.279

Alfa AF: 0.337 Hom.: 3045

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
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs1264320; hg19: chr6-30861000; COSMIC: COSV61318543; COSMIC: COSV61318543;