6-30897948-C-T

Variant names:

• chr6-30897948-C-T
• rs2239518
• NM_001297654.2:c.2217-125C>T

Variant summary

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

The NM_001297654.2(DDR1):​c.2217-125C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.222 in 710,530 control chromosomes in the GnomAD database, including 22,834 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 0.20 (3969 hom., cov: 32)
  • Exomes 𝑓: 0.23 (18865 hom.)
• Consequence: DDR1 NM_001297654.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.37
• Publications: 19 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=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.553 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDR1	NM_001297654.2	MANE Select	c.2217-125C>T		intron	N/A	NP_001284583.1	Q08345-1
	DDR1	NM_001387892.1		c.2235-125C>T		intron	N/A	NP_001374821.1	Q08345-5
	DDR1	NM_013994.3		c.2235-125C>T		intron	N/A	NP_054700.2	Q08345-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDR1	ENST00000376568.8	TSL:1 MANE Select	c.2217-125C>T		intron	N/A	ENSP00000365752.3	Q08345-1
	DDR1	ENST00000452441.5	TSL:1	c.2217-125C>T		intron	N/A	ENSP00000405039.1	Q08345-1
	DDR1	ENST00000376567.6	TSL:1	c.2106-125C>T		intron	N/A	ENSP00000365751.2	Q08345-2

Frequencies

GnomAD3 genomes AF: 0.203 AC: 30801 AN: 152028 Hom.: 3957 Cov.: 32

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.293

Gnomad AMR AF: 0.329

Gnomad ASJ AF: 0.203

Gnomad EAS AF: 0.570

Gnomad SAS AF: 0.420

Gnomad FIN AF: 0.240

Gnomad MID AF: 0.166

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.192

GnomAD4 exome AF: 0.227 AC: 126736 AN: 558384 Hom.: 18865 AF XY: 0.234 AC XY: 68513 AN XY: 293228

African (AFR) AF: 0.136 AC: 2074 AN: 15260

American (AMR) AF: 0.413 AC: 11193 AN: 27098

Ashkenazi Jewish (ASJ) AF: 0.211 AC: 3332 AN: 15820

East Asian (EAS) AF: 0.561 AC: 17868 AN: 31868

South Asian (SAS) AF: 0.391 AC: 20728 AN: 53044

European-Finnish (FIN) AF: 0.246 AC: 8744 AN: 35520

Middle Eastern (MID) AF: 0.196 AC: 712 AN: 3632

European-Non Finnish (NFE) AF: 0.160 AC: 55237 AN: 346222

Other (OTH) AF: 0.229 AC: 6848 AN: 29920

GnomAD4 genome AF: 0.203 AC: 30833 AN: 152146 Hom.: 3969 Cov.: 32 AF XY: 0.213 AC XY: 15846 AN XY: 74390

African (AFR) AF: 0.142 AC: 5904 AN: 41524

American (AMR) AF: 0.329 AC: 5030 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.203 AC: 705 AN: 3472

East Asian (EAS) AF: 0.570 AC: 2937 AN: 5150

South Asian (SAS) AF: 0.419 AC: 2019 AN: 4824

European-Finnish (FIN) AF: 0.240 AC: 2538 AN: 10588

Middle Eastern (MID) AF: 0.171 AC: 50 AN: 292

European-Non Finnish (NFE) AF: 0.161 AC: 10959 AN: 67976

Other (OTH) AF: 0.200 AC: 424 AN: 2116

Alfa AF: 0.180 Hom.: 10787

Bravo AF: 0.203

Asia WGS AF: 0.495 AC: 1718 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	1.9
DANN	Benign	0.66
PhyloP100		-1.4
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: rs2239518; hg19: chr6-30865725; COSMIC: COSV61322506; COSMIC: COSV61322506;