chr6-30887474-G-A

Variant names:

• chr6-30887474-G-A
• rs4618569
• NM_001297654.2:c.-42-1214G>A

Variant summary

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

The NM_001297654.2(DDR1):​c.-42-1214G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.262 in 151,858 control chromosomes in the GnomAD database, including 6,162 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 (6162 hom., cov: 32)
• Consequence: DDR1 NM_001297654.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.364
• Publications: 26 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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.595 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001297654.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDR1	NM_001297654.2	MANE Select	c.-42-1214G>A		intron	N/A	NP_001284583.1
	DDR1	NM_001387892.1		c.-42-1214G>A		intron	N/A	NP_001374821.1
	DDR1	NM_013994.3		c.-42-1214G>A		intron	N/A	NP_054700.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDR1	ENST00000376568.8	TSL:1 MANE Select	c.-42-1214G>A		intron	N/A	ENSP00000365752.3
	DDR1	ENST00000452441.5	TSL:1	c.-42-1214G>A		intron	N/A	ENSP00000405039.1
	DDR1	ENST00000376570.8	TSL:1	c.-42-1214G>A		intron	N/A	ENSP00000365754.4

Frequencies

GnomAD3 genomes AF: 0.262 AC: 39729 AN: 151740 Hom.: 6146 Cov.: 32

Gnomad AFR AF: 0.273

Gnomad AMI AF: 0.301

Gnomad AMR AF: 0.365

Gnomad ASJ AF: 0.266

Gnomad EAS AF: 0.612

Gnomad SAS AF: 0.541

Gnomad FIN AF: 0.257

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.259

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.262 AC: 39770 AN: 151858 Hom.: 6162 Cov.: 32 AF XY: 0.273 AC XY: 20240 AN XY: 74200

African (AFR) AF: 0.272 AC: 11270 AN: 41364

American (AMR) AF: 0.365 AC: 5578 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.266 AC: 923 AN: 3470

East Asian (EAS) AF: 0.613 AC: 3167 AN: 5170

South Asian (SAS) AF: 0.541 AC: 2598 AN: 4806

European-Finnish (FIN) AF: 0.257 AC: 2698 AN: 10492

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.186 AC: 12632 AN: 67970

Other (OTH) AF: 0.268 AC: 565 AN: 2112

Alfa AF: 0.220 Hom.: 11243

Bravo AF: 0.266

Asia WGS AF: 0.580 AC: 2007 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.26
DANN	Benign	0.40
PhyloP100		-0.36
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4618569; hg19: chr6-30855251;