Variant 6-30893089-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001297654.2(DDR1):c.1121C>A(p.Pro374Gln) 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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.18

Variant links:

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 links:

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ACMG classification

Classification made for transcript

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=0.05239594).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDR1	NM_001297654.2 link	c.1121C>A	p.Pro374Gln	missense_variant	Exon 9 of 18	ENST00000376568.8	NP_001284583.1	Q08345-1A0A024RCL1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDR1	ENST00000376568.8 link	c.1121C>A	p.Pro374Gln	missense_variant	Exon 9 of 18	1	NM_001297654.2	ENSP00000365752.3		Q08345-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000800

AC:

AN:

250026

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

135282

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000881

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460130

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726434

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.090

BayesDel_noAF

Benign

-0.37

CADD

Benign

5.9

DANN

Benign

0.82

DEOGEN2

Benign

0.11

T;.;.;.;.;T;T;.;.;T;.;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.050

LIST_S2

Benign

0.61

.;.;.;.;.;.;.;.;.;.;T;.

M_CAP

Benign

0.031

MetaRNN

Benign

0.052

T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

1.1

L;L;L;L;L;L;L;.;L;.;L;.

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.57

N;N;N;N;N;N;N;N;N;.;N;N

REVEL

Benign

0.20

Sift

Benign

0.55

T;T;T;T;T;T;T;T;T;.;T;T

Sift4G

Benign

0.67

T;T;T;T;T;T;T;T;T;T;T;T

Polyphen

0.026

B;.;.;.;.;B;B;.;.;.;B;B

Vest4

0.22

MutPred

0.23

Loss of glycosylation at S373 (P = 0.061);Loss of glycosylation at S373 (P = 0.061);Loss of glycosylation at S373 (P = 0.061);Loss of glycosylation at S373 (P = 0.061);Loss of glycosylation at S373 (P = 0.061);Loss of glycosylation at S373 (P = 0.061);Loss of glycosylation at S373 (P = 0.061);.;Loss of glycosylation at S373 (P = 0.061);Loss of glycosylation at S373 (P = 0.061);Loss of glycosylation at S373 (P = 0.061);.;

MVP

0.53

ClinPred

0.052

GERP RS

-6.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.028

gMVP

0.34

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over