ENST00000505066.5:c.-43+1227G>C

Variant names:

• chr6-30877786-G-C
• rs1264332
• ENST00000505066.5:c.-43+1227G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000505066.5(DDR1):​c.-43+1227G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.28 in 152,066 control chromosomes in the GnomAD database, including 6,843 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 (6843 hom., cov: 32)
• Consequence: DDR1 ENST00000505066.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.307
• Publications: 15 publications found

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

ACMG classification

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 = 0.358 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDR1	ENST00000505066.5	c.-43+1227G>C		intron_variant	Intron 1 of 3	4		ENSP00000421189.1
DDR1	ENST00000502955.5	c.-271+1227G>C		intron_variant	Intron 1 of 3	4		ENSP00000424346.1

Frequencies

GnomAD3 genomes AF: 0.280 AC: 42506 AN: 151948 Hom.: 6845 Cov.: 32

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.309

Gnomad AMR AF: 0.244

Gnomad ASJ AF: 0.391

Gnomad EAS AF: 0.257

Gnomad SAS AF: 0.265

Gnomad FIN AF: 0.393

Gnomad MID AF: 0.360

Gnomad NFE AF: 0.361

Gnomad OTH AF: 0.278

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.280 AC: 42515 AN: 152066 Hom.: 6843 Cov.: 32 AF XY: 0.281 AC XY: 20889 AN XY: 74328

African (AFR) AF: 0.124 AC: 5123 AN: 41472

American (AMR) AF: 0.245 AC: 3741 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.391 AC: 1358 AN: 3470

East Asian (EAS) AF: 0.257 AC: 1327 AN: 5170

South Asian (SAS) AF: 0.264 AC: 1274 AN: 4818

European-Finnish (FIN) AF: 0.393 AC: 4159 AN: 10570

Middle Eastern (MID) AF: 0.360 AC: 105 AN: 292

European-Non Finnish (NFE) AF: 0.361 AC: 24564 AN: 67958

Other (OTH) AF: 0.276 AC: 582 AN: 2110

Alfa AF: 0.320 Hom.: 1213

Bravo AF: 0.262

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.5
DANN	Benign	0.53
PhyloP100		-0.31

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1264332; hg19: chr6-30845563;