6-30889004-A-T

Variant names:

• chr6-30889004-A-T
• NM_001297654.2:c.182A>T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001297654.2(DDR1):​c.182A>T​(p.His61Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DDR1 NM_001297654.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.14

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 Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.875

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDR1	NM_001297654.2	c.182A>T	p.His61Leu	missense_variant	Exon 3 of 18	ENST00000376568.8	NP_001284583.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDR1	ENST00000376568.8	c.182A>T	p.His61Leu	missense_variant	Exon 3 of 18	1	NM_001297654.2	ENSP00000365752.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.82
BayesDel_addAF	Pathogenic	0.47	D
BayesDel_noAF	Pathogenic	0.44
CADD	Uncertain	25
DANN	Benign	0.96
DEOGEN2	Uncertain	0.61	D;D;D;.;.;.;T;T;.;D;.;D;T;.;D;.;D;.;.;D;D;D;D;.;T;D;D;D;.;.;T;.;.
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.86	D;D;.;T;D;.;D;D;D;D;.;.;D;D;.;D;D;.;.;D;D;.;.;.;D;.;D;D;D;.;.;.;D
M_CAP	Pathogenic	0.72	D
MetaRNN	Pathogenic	0.87	D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM	Pathogenic	1.1	D
MutationAssessor	Benign	0.79	.;.;N;.;.;N;.;.;.;.;N;.;.;.;.;.;.;N;N;.;.;N;N;.;.;.;.;.;.;N;.;N;N
PrimateAI	Uncertain	0.54	T
PROVEAN	Pathogenic	-6.9	D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
REVEL	Pathogenic	0.90
Sift	Uncertain	0.0030	D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;T;D;D;D;D;D;D;D;D;D;D;D;D;D
Sift4G	Benign	0.21	T;T;D;T;T;D;T;D;D;T;D;T;D;T;T;D;T;D;D;T;T;D;D;D;T;T;T;T;T;D;D;T;D
Polyphen		1.0, 0.54, 0.97	.;.;D;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;D;D;.;.;.;.;.;.;.;.;P;D
Vest4		0.58, 0.56, 0.54, 0.56, 0.58, 0.57, 0.47, 0.56, 0.70, 0.56
MutPred		0.59		Gain of stability (P = 0.0917);Gain of stability (P = 0.0917);Gain of stability (P = 0.0917);Gain of stability (P = 0.0917);Gain of stability (P = 0.0917);Gain of stability (P = 0.0917);Gain of stability (P = 0.0917);Gain of stability (P = 0.0917);Gain of stability (P = 0.0917);Gain of stability (P = 0.0917);Gain of stability (P = 0.0917);Gain of stability (P = 0.0917);Gain of stability (P = 0.0917);Gain of stability (P = 0.0917);Gain of stability (P = 0.0917);Gain of stability (P = 0.0917);Gain of stability (P = 0.0917);Gain of stability (P = 0.0917);Gain of stability (P = 0.0917);Gain of stability (P = 0.0917);Gain of stability (P = 0.0917);Gain of stability (P = 0.0917);Gain of stability (P = 0.0917);.;Gain of stability (P = 0.0917);Gain of stability (P = 0.0917);Gain of stability (P = 0.0917);Gain of stability (P = 0.0917);.;Gain of stability (P = 0.0917);Gain of stability (P = 0.0917);Gain of stability (P = 0.0917);Gain of stability (P = 0.0917);
MVP		0.94
MPC		0.68
ClinPred		0.96	D
GERP RS		5.1
Varity_R		0.89
gMVP		0.83

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-30856781;