6-30888778-A-T

Variant names:

• chr6-30888778-A-T
• rs55901302
• NM_001297654.2:c.49A>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001297654.2(DDR1):​c.49A>T​(p.Ser17Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S17G) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DDR1 NM_001297654.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.148
• Publications: 6 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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15950361).

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.49A>T	p.Ser17Cys	missense	Exon 2 of 18	NP_001284583.1	Q08345-1
	DDR1	NM_001387892.1		c.49A>T	p.Ser17Cys	missense	Exon 2 of 18	NP_001374821.1	Q08345-5
	DDR1	NM_013994.3		c.49A>T	p.Ser17Cys	missense	Exon 2 of 18	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.49A>T	p.Ser17Cys	missense	Exon 2 of 18	ENSP00000365752.3	Q08345-1
	DDR1	ENST00000452441.5	TSL:1	c.49A>T	p.Ser17Cys	missense	Exon 3 of 19	ENSP00000405039.1	Q08345-1
	DDR1	ENST00000376567.6	TSL:1	c.49A>T	p.Ser17Cys	missense	Exon 1 of 16	ENSP00000365751.2	Q08345-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Benign	15
DANN	Benign	0.87
DEOGEN2	Benign	0.025	T
Eigen	Benign	-0.79
Eigen_PC	Benign	-0.78
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.072	D
MetaRNN	Benign	0.16	T
MetaSVM	Uncertain	0.40	D
MutationAssessor	Benign	1.1	L
PhyloP100		-0.15
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-1.8	N
REVEL	Uncertain	0.46
Sift	Benign	0.096	T
Sift4G	Uncertain	0.017	D
Polyphen		0.070	B
Vest4		0.12
MutPred		0.32		Loss of disorder (P = 0.0326)
MVP		0.83
MPC		0.71
ClinPred		0.40	T
GERP RS		-0.81
PromoterAI		-0.030	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.047
gMVP		0.55
Mutation Taster		=93/7	polymorphism

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: rs55901302; hg19: chr6-30856555;