6-30893089-C-G

Variant names:

• chr6-30893089-C-G
• rs200571528
• NM_001297654.2:c.1121C>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001297654.2(DDR1):​c.1121C>G​(p.Pro374Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,130 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: DDR1 NM_001297654.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.067843705).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDR1	NM_001297654.2	c.1121C>G	p.Pro374Arg	missense_variant	Exon 9 of 18	ENST00000376568.8	NP_001284583.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDR1	ENST00000376568.8	c.1121C>G	p.Pro374Arg	missense_variant	Exon 9 of 18	1	NM_001297654.2	ENSP00000365752.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460130 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726434

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.046	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	6.2
DANN	Benign	0.73
DEOGEN2	Benign	0.12	T;.;.;.;.;T;T;.;.;T;.;T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.052	N
LIST_S2	Benign	0.81	.;.;.;.;.;.;.;.;.;.;T;.
M_CAP	Benign	0.051	D
MetaRNN	Benign	0.068	T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	1.1	L;L;L;L;L;L;L;.;L;.;L;.
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.81	N;N;N;N;N;N;N;N;N;.;N;N
REVEL	Benign	0.24
Sift	Benign	0.52	T;T;T;T;T;T;T;T;T;.;T;T
Sift4G	Benign	0.69	T;T;T;T;T;T;T;T;T;T;T;T
Polyphen		0.026	B;.;.;.;.;B;B;.;.;.;B;D
Vest4		0.25
MutPred		0.30		Loss of glycosylation at S372 (P = 0.0573);Loss of glycosylation at S372 (P = 0.0573);Loss of glycosylation at S372 (P = 0.0573);Loss of glycosylation at S372 (P = 0.0573);Loss of glycosylation at S372 (P = 0.0573);Loss of glycosylation at S372 (P = 0.0573);Loss of glycosylation at S372 (P = 0.0573);.;Loss of glycosylation at S372 (P = 0.0573);Loss of glycosylation at S372 (P = 0.0573);Loss of glycosylation at S372 (P = 0.0573);.;
MVP		0.56
ClinPred		0.077	T
GERP RS		-6.8
Varity_R		0.025
gMVP		0.47

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: rs200571528; hg19: chr6-30860866;