rs1264327

Positions:

• chr6-30882805-G-A

Variant summary

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

The ENST00000418800.6(DDR1):​c.-221G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.256 in 152,486 control chromosomes in the GnomAD database, including 6,154 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 0.26 (6134 hom., cov: 33)
  • Exomes 𝑓: 0.36 (20 hom.)
• Consequence: DDR1 ENST00000418800.6 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.817

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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.347 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DDR1	NM_001387893.1	c.-43+1680G>A		intron_variant			NP_001374822.1
DDR1	NM_001387908.1	c.-43+1680G>A		intron_variant			NP_001374837.1
DDR1	NM_001387909.1	c.-99+1680G>A		intron_variant			NP_001374838.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DDR1	ENST00000418800.6	c.-221G>A		5_prime_UTR_variant	1/17	2		ENSP00000407699
DDR1	ENST00000324771.12	c.-272+1680G>A		intron_variant		5		ENSP00000318217	P1
DDR1	ENST00000460944.6	c.-43+1680G>A		intron_variant		5		ENSP00000426420

Frequencies

GnomAD3 genomes AF: 0.256 AC: 38914 AN: 152056 Hom.: 6138 Cov.: 33

Gnomad AFR AF: 0.0781

Gnomad AMI AF: 0.288

Gnomad AMR AF: 0.227

Gnomad ASJ AF: 0.385

Gnomad EAS AF: 0.188

Gnomad SAS AF: 0.216

Gnomad FIN AF: 0.390

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.350

Gnomad OTH AF: 0.254

GnomAD4 exome AF: 0.359 AC: 112 AN: 312 Hom.: 20 Cov.: 0 AF XY: 0.341 AC XY: 60 AN XY: 176

Gnomad4 AMR exome AF: 0.00

Gnomad4 EAS exome AF: 0.200

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.414

Gnomad4 NFE exome AF: 0.311

Gnomad4 OTH exome AF: 0.188

GnomAD4 genome AF: 0.256 AC: 38907 AN: 152174 Hom.: 6134 Cov.: 33 AF XY: 0.256 AC XY: 19039 AN XY: 74408

Gnomad4 AFR AF: 0.0780

Gnomad4 AMR AF: 0.228

Gnomad4 ASJ AF: 0.385

Gnomad4 EAS AF: 0.188

Gnomad4 SAS AF: 0.215

Gnomad4 FIN AF: 0.390

Gnomad4 NFE AF: 0.350

Gnomad4 OTH AF: 0.251

Alfa AF: 0.337 Hom.: 6110

Bravo AF: 0.237

Asia WGS AF: 0.158 AC: 554 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	17
DANN	Benign	0.76

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: rs1264327; hg19: chr6-30850582;