Genetic Variant DDR1:c.2217-125C>T (chr6-30897948-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001297654.2(DDR1):c.2217-125C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.222 in 710,530 control chromosomes in the GnomAD database, including 22,834 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.20 ( 3969 hom., cov: 32)

Exomes 𝑓: 0.23 ( 18865 hom. )

Consequence

DDR1
NM_001297654.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.37

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 was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.553 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDR1	NM_001297654.2 link	c.2217-125C>T		intron_variant	Intron 15 of 17	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.2217-125C>T		intron_variant	Intron 15 of 17	1	NM_001297654.2	ENSP00000365752.3		Q08345-1

Frequencies

GnomAD3 genomes

AF:

0.203

AC:

30801

AN:

152028

Hom.:

3957

Cov.:

show subpopulations

Gnomad AFR

AF:

0.142

Gnomad AMI

AF:

0.293

Gnomad AMR

AF:

0.329

Gnomad ASJ

AF:

0.203

Gnomad EAS

AF:

0.570

Gnomad SAS

AF:

0.420

Gnomad FIN

AF:

0.240

Gnomad MID

AF:

0.166

Gnomad NFE

AF:

0.161

Gnomad OTH

AF:

0.192

GnomAD4 exome

AF:

0.227

AC:

126736

AN:

558384

Hom.:

18865

AF XY:

0.234

AC XY:

68513

AN XY:

293228

show subpopulations

African (AFR)

AF:

0.136

AC:

2074

AN:

15260

American (AMR)

AF:

0.413

AC:

11193

AN:

27098

Ashkenazi Jewish (ASJ)

AF:

0.211

AC:

3332

AN:

15820

East Asian (EAS)

AF:

0.561

AC:

17868

AN:

31868

South Asian (SAS)

AF:

0.391

AC:

20728

AN:

53044

European-Finnish (FIN)

AF:

0.246

AC:

8744

AN:

35520

Middle Eastern (MID)

AF:

0.196

AC:

712

AN:

3632

European-Non Finnish (NFE)

AF:

0.160

AC:

55237

AN:

346222

Other (OTH)

AF:

0.229

AC:

6848

AN:

29920

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

5371

10743

16114

21486

26857

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.203

AC:

30833

AN:

152146

Hom.:

3969

Cov.:

AF XY:

0.213

AC XY:

15846

AN XY:

74390

show subpopulations

African (AFR)

AF:

0.142

AC:

5904

AN:

41524

American (AMR)

AF:

0.329

AC:

5030

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.203

AC:

705

AN:

3472

East Asian (EAS)

AF:

0.570

AC:

2937

AN:

5150

South Asian (SAS)

AF:

0.419

AC:

2019

AN:

4824

European-Finnish (FIN)

AF:

0.240

AC:

2538

AN:

10588

Middle Eastern (MID)

AF:

0.171

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.161

AC:

10959

AN:

67976

Other (OTH)

AF:

0.200

AC:

424

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1188

2376

3565

4753

5941

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.180

Hom.:

10787

Bravo

AF:

0.203

Asia WGS

AF:

0.495

AC:

1718

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

1.9

(source)

DANN

Benign

0.66

PhyloP100

-1.4

Mutation Taster

=100/0

polymorphism (auto)

(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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chr6-30897948-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

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