rs1264333

Positions:

• chr6-30876537-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000505066.5(DDR1):​c.-65T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.28 in 152,116 control chromosomes in the GnomAD database, including 6,848 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 (6848 hom., cov: 32)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: DDR1 ENST00000505066.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.666

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=-0.82).
• 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	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DDR1	ENST00000502955.5	c.-293T>C		5_prime_UTR_variant	1/4	4		ENSP00000424346
DDR1	ENST00000505066.5	c.-65T>C		5_prime_UTR_variant	1/4	4		ENSP00000421189

Frequencies

GnomAD3 genomes AF: 0.280 AC: 42584 AN: 151994 Hom.: 6850 Cov.: 32

Gnomad AFR AF: 0.124

Gnomad AMI AF: 0.292

Gnomad AMR AF: 0.245

Gnomad ASJ AF: 0.391

Gnomad EAS AF: 0.256

Gnomad SAS AF: 0.265

Gnomad FIN AF: 0.392

Gnomad MID AF: 0.379

Gnomad NFE AF: 0.362

Gnomad OTH AF: 0.279

GnomAD4 exome AF: 0.500 AC: 1 AN: 2 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

Gnomad4 FIN exome AF: 0.500

GnomAD4 genome AF: 0.280 AC: 42593 AN: 152114 Hom.: 6848 Cov.: 32 AF XY: 0.281 AC XY: 20907 AN XY: 74350

Gnomad4 AFR AF: 0.125

Gnomad4 AMR AF: 0.245

Gnomad4 ASJ AF: 0.391

Gnomad4 EAS AF: 0.256

Gnomad4 SAS AF: 0.264

Gnomad4 FIN AF: 0.392

Gnomad4 NFE AF: 0.362

Gnomad4 OTH AF: 0.276

Alfa AF: 0.354 Hom.: 13962

Bravo AF: 0.263

Asia WGS AF: 0.213 AC: 744 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	15
DANN	Benign	0.65

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1264333; hg19: chr6-30844314;