dbSNP rs1264333: DDR1:c.-65T>C (chr6-30876537-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000505066.5(DDR1):c.-65T>C variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.28 in 152,116 control chromosomes in the GnomAD database, including 6,848 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 0.28 ( 6848 hom., cov: 32)

Exomes 𝑓: 0.50 ( 0 hom. )

Consequence

DDR1
ENST00000505066.5 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.666

Publications

28 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:

Genome browser will be placed here

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=-0.82).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.358 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein
DDR1	ENST00000505066.5 link	c.-65T>C	5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 4	4	ENSP00000421189.1
DDR1	ENST00000502955.5 link	c.-293T>C	5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 4	4	ENSP00000424346.1
DDR1	ENST00000505066.5 link	c.-65T>C	5_prime_UTR_variant	Exon 1 of 4	4	ENSP00000421189.1
DDR1	ENST00000502955.5 link	c.-293T>C	5_prime_UTR_variant	Exon 1 of 4	4	ENSP00000424346.1

Frequencies

GnomAD3 genomes

AF:

0.280

AC:

42584

AN:

151994

Hom.:

6850

Cov.:

show subpopulations

Gnomad AFR

AF:

0.124

Gnomad AMI

AF:

0.292

Gnomad AMR

AF:

0.245

Gnomad ASJ

AF:

0.391

Gnomad EAS

AF:

0.256

Gnomad SAS

AF:

0.265

Gnomad FIN

AF:

0.392

Gnomad MID

AF:

0.379

Gnomad NFE

AF:

0.362

Gnomad OTH

AF:

0.279

GnomAD4 exome

AF:

0.500

AC:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.280

AC:

42593

AN:

152114

Hom.:

6848

Cov.:

AF XY:

0.281

AC XY:

20907

AN XY:

74350

show subpopulations

African (AFR)

AF:

0.125

AC:

5175

AN:

41534

American (AMR)

AF:

0.245

AC:

3743

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.391

AC:

1358

AN:

3470

East Asian (EAS)

AF:

0.256

AC:

1324

AN:

5176

South Asian (SAS)

AF:

0.264

AC:

1276

AN:

4830

European-Finnish (FIN)

AF:

0.392

AC:

4139

AN:

10546

Middle Eastern (MID)

AF:

0.378

AC:

111

AN:

294

European-Non Finnish (NFE)

AF:

0.362

AC:

24621

AN:

67980

Other (OTH)

AF:

0.276

AC:

581

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1505

3010

4516

6021

7526

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

442

884

1326

1768

2210

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.336

Hom.:

33158

Bravo

AF:

0.263

Asia WGS

AF:

0.213

AC:

744

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

(source)

DANN

Benign

0.65

PhyloP100

0.67

PromoterAI

0.013

Neutral

(source)

Splicing

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over