chr6-30892329-C-G

Variant names:

• chr6-30892329-C-G
• rs780397649
• NM_001297654.2:c.886C>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001297654.2(DDR1):​c.886C>G​(p.Arg296Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: DDR1 NM_001297654.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.63

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDR1	NM_001297654.2	c.886C>G	p.Arg296Gly	missense_variant	Exon 8 of 18	ENST00000376568.8	NP_001284583.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDR1	ENST00000376568.8	c.886C>G	p.Arg296Gly	missense_variant	Exon 8 of 18	1	NM_001297654.2	ENSP00000365752.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.040
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.36	T;.;.;.;.;T;T;.;.;T;.;T
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.85	.;.;.;.;.;.;.;.;.;.;D;.
M_CAP	Uncertain	0.13	D
MetaRNN	Uncertain	0.74	D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM	Benign	-0.63	T
MutationAssessor	Benign	1.7	L;L;L;L;L;L;L;.;L;.;L;.
PrimateAI	Uncertain	0.75	T
PROVEAN	Uncertain	-3.8	D;D;D;D;D;D;D;D;D;.;D;D
REVEL	Uncertain	0.43
Sift	Uncertain	0.0030	D;D;D;D;D;D;D;D;D;.;D;D
Sift4G	Uncertain	0.011	D;D;D;D;D;D;D;D;D;D;D;D
Polyphen		0.96	D;.;.;.;.;D;D;.;.;.;D;D
Vest4		0.61
MutPred		0.41		Loss of MoRF binding (P = 0.0101);Loss of MoRF binding (P = 0.0101);Loss of MoRF binding (P = 0.0101);Loss of MoRF binding (P = 0.0101);Loss of MoRF binding (P = 0.0101);Loss of MoRF binding (P = 0.0101);Loss of MoRF binding (P = 0.0101);.;Loss of MoRF binding (P = 0.0101);Loss of MoRF binding (P = 0.0101);Loss of MoRF binding (P = 0.0101);.;
MVP		0.81
ClinPred		0.99	D
GERP RS		4.5
Varity_R		0.61
gMVP		0.79

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

LitVar

Other links and lift over

dbSNP: rs780397649; hg19: chr6-30860106;