6-30893088-CC-TT

Variant names:

• chr6-30893088-CC-TT
• NM_001297654.2:c.1120_1121delCCinsTT
• DDR1 p.Pro374Leu

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001297654.2(DDR1):​c.1120_1121delCCinsTT​(p.Pro374Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: DDR1 NM_001297654.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.532
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

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.1120_1121delCCinsTT	p.Pro374Leu	missense	N/A	NP_001284583.1	Q08345-1
	DDR1	NM_001387892.1		c.1120_1121delCCinsTT	p.Pro374Leu	missense	N/A	NP_001374821.1	Q08345-5
	DDR1	NM_013994.3		c.1120_1121delCCinsTT	p.Pro374Leu	missense	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.1120_1121delCCinsTT	p.Pro374Leu	missense	N/A	ENSP00000365752.3	Q08345-1
	DDR1	ENST00000452441.5	TSL:1	c.1120_1121delCCinsTT	p.Pro374Leu	missense	N/A	ENSP00000405039.1	Q08345-1
	DDR1	ENST00000376567.6	TSL:1	c.1120_1121delCCinsTT	p.Pro374Leu	missense	N/A	ENSP00000365751.2	Q08345-2

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.53

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr6-30860865;