dbSNP rs1264327: DDR1:c.-221G>A (chr6-30882805-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001387893.1(DDR1):c.-43+1680G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.256 in 152,486 control chromosomes in the GnomAD database, including 6,154 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 0.26 ( 6134 hom., cov: 33)

Exomes 𝑓: 0.36 ( 20 hom. )

Consequence

DDR1
NM_001387893.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.817

Publications

14 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=-0.8).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.347 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001387893.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein	UniProt
DDR1	NM_001387893.1	c.-43+1680G>A	intron	N/A	NP_001374822.1	Q08345-1
DDR1	NM_001387908.1	c.-43+1680G>A	intron	N/A	NP_001374837.1	A0A024RCQ1
DDR1	NM_001387909.1	c.-99+1680G>A	intron	N/A	NP_001374838.1	A0A024RCQ1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DDR1	ENST00000418800.6	TSL:2	c.-221G>A	5_prime_UTR	Exon 1 of 17	ENSP00000407699.2	Q08345-2
DDR1	ENST00000324771.12	TSL:5	c.-272+1680G>A	intron	N/A	ENSP00000318217.8	Q08345-1
DDR1	ENST00000908926.1		c.-43+812G>A	intron	N/A	ENSP00000578985.1

Frequencies

GnomAD3 genomes

AF:

0.256

AC:

38914

AN:

152056

Hom.:

6138

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0781

Gnomad AMI

AF:

0.288

Gnomad AMR

AF:

0.227

Gnomad ASJ

AF:

0.385

Gnomad EAS

AF:

0.188

Gnomad SAS

AF:

0.216

Gnomad FIN

AF:

0.390

Gnomad MID

AF:

0.326

Gnomad NFE

AF:

0.350

Gnomad OTH

AF:

0.254

GnomAD4 exome

AF:

0.359

AC:

112

AN:

312

Hom.:

Cov.:

AF XY:

0.341

AC XY:

AN XY:

176

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.200

AC:

AN:

South Asian (SAS)

AF:

0.500

AC:

AN:

European-Finnish (FIN)

AF:

0.414

AC:

AN:

174

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.311

AC:

AN:

106

Other (OTH)

AF:

0.188

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.256

AC:

38907

AN:

152174

Hom.:

6134

Cov.:

AF XY:

0.256

AC XY:

19039

AN XY:

74408

show subpopulations

African (AFR)

AF:

0.0780

AC:

3239

AN:

41536

American (AMR)

AF:

0.228

AC:

3480

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.385

AC:

1335

AN:

3470

East Asian (EAS)

AF:

0.188

AC:

973

AN:

5176

South Asian (SAS)

AF:

0.215

AC:

1036

AN:

4822

European-Finnish (FIN)

AF:

0.390

AC:

4136

AN:

10594

Middle Eastern (MID)

AF:

0.323

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.350

AC:

23818

AN:

67962

Other (OTH)

AF:

0.251

AC:

532

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1431

2862

4293

5724

7155

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

406

812

1218

1624

2030

<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:

0.331

Hom.:

10838

Bravo

AF:

0.237

Asia WGS

AF:

0.158

AC:

554

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

(source)

DANN

Benign

0.76

PhyloP100

0.82

PromoterAI

-0.026

Neutral

(source)

Mutation Taster

=295/5

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over