rs9468843

Variant names:

• chr6-30900181-T-C
• rs9468843
• NM_001297654.2:c.*885T>C

Your query was ambiguous. Multiple possible variants found:

• chr6-30900181-T-C
• chr6-30900181-T-G

Variant summary

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

The NM_001297654.2(DDR1):​c.*885T>C variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 508,590 control chromosomes in the GnomAD database, including 14,765 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 0.17 (2925 hom., cov: 32)
  • Exomes 𝑓: 0.23 (11840 hom.)
• Consequence: DDR1 NM_001297654.2 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.23

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=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.385 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDR1	NM_001297654.2	c.*885T>C		downstream_gene_variant		ENST00000376568.8	NP_001284583.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDR1	ENST00000376568.8	c.*885T>C		downstream_gene_variant		1	NM_001297654.2	ENSP00000365752.3

Frequencies

GnomAD3 genomes AF: 0.173 AC: 26340 AN: 152006 Hom.: 2910 Cov.: 32

Gnomad AFR AF: 0.0880

Gnomad AMI AF: 0.292

Gnomad AMR AF: 0.295

Gnomad ASJ AF: 0.203

Gnomad EAS AF: 0.371

Gnomad SAS AF: 0.401

Gnomad FIN AF: 0.223

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.156

Gnomad OTH AF: 0.172

GnomAD4 exome AF: 0.227 AC: 80751 AN: 356466 Hom.: 11840 Cov.: 0 AF XY: 0.236 AC XY: 46307 AN XY: 196526

Gnomad4 AFR exome AF: 0.0867

Gnomad4 AMR exome AF: 0.391

Gnomad4 ASJ exome AF: 0.204

Gnomad4 EAS exome AF: 0.394

Gnomad4 SAS exome AF: 0.374

Gnomad4 FIN exome AF: 0.218

Gnomad4 NFE exome AF: 0.154

Gnomad4 OTH exome AF: 0.207

GnomAD4 genome AF: 0.173 AC: 26369 AN: 152124 Hom.: 2925 Cov.: 32 AF XY: 0.184 AC XY: 13687 AN XY: 74360

Gnomad4 AFR AF: 0.0878

Gnomad4 AMR AF: 0.295

Gnomad4 ASJ AF: 0.203

Gnomad4 EAS AF: 0.372

Gnomad4 SAS AF: 0.400

Gnomad4 FIN AF: 0.223

Gnomad4 NFE AF: 0.156

Gnomad4 OTH AF: 0.180

Alfa AF: 0.164 Hom.: 1436

Bravo AF: 0.171

Asia WGS AF: 0.439 AC: 1526 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.4
DANN	Benign	0.46

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9468843; hg19: chr6-30867958; COSMIC: COSV61319151;