Genetic Variant NM_001297654.2:c.886C>A (chr6-30892329-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_001297654.2(DDR1):c.886C>A(p.Arg296Ser) 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R296C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

DDR1
NM_001297654.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.63

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

chondrodysplasia
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

DDR1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DDR1	NM_001297654.2	MANE Select	c.886C>A	p.Arg296Ser	missense	Exon 8 of 18	NP_001284583.1	Q08345-1
DDR1	NM_001387892.1		c.886C>A	p.Arg296Ser	missense	Exon 8 of 18	NP_001374821.1	Q08345-5
DDR1	NM_013994.3		c.886C>A	p.Arg296Ser	missense	Exon 8 of 18	NP_054700.2	Q08345-5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DDR1	ENST00000376568.8	TSL:1 MANE Select	c.886C>A	p.Arg296Ser	missense	Exon 8 of 18	ENSP00000365752.3	Q08345-1
DDR1	ENST00000452441.5	TSL:1	c.886C>A	p.Arg296Ser	missense	Exon 9 of 19	ENSP00000405039.1	Q08345-1
DDR1	ENST00000376567.6	TSL:1	c.886C>A	p.Arg296Ser	missense	Exon 7 of 16	ENSP00000365751.2	Q08345-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1421866

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

702732

African (AFR)

AF:

0.00

AC:

AN:

32806

American (AMR)

AF:

0.00

AC:

AN:

42280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23776

East Asian (EAS)

AF:

0.00

AC:

AN:

39284

South Asian (SAS)

AF:

0.00

AC:

AN:

81180

European-Finnish (FIN)

AF:

0.00

AC:

AN:

46788

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5582

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1091426

Other (OTH)

AF:

0.00

AC:

AN:

58744

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.30

BayesDel_addAF

Uncertain

0.16

BayesDel_noAF

Uncertain

-0.010

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.21

Eigen

Uncertain

0.37

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.85

M_CAP

Benign

0.062

MetaRNN

Uncertain

0.48

MetaSVM

Benign

-0.63

MutationAssessor

Benign

1.4

PhyloP100

2.6

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-2.2

REVEL

Uncertain

0.30

Sift

Uncertain

0.0040

Sift4G

Benign

0.080

Polyphen

0.92

Vest4

0.40

MutPred

0.41

Loss of MoRF binding (P = 0.015)

MVP

0.84

ClinPred

0.83

GERP RS

4.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.61

gMVP

0.70

Mutation Taster

=68/32

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over