6-30879053-G-T

Variant names:

• chr6-30879053-G-T
• rs1264331
• ENST00000505066.5:c.-43+2494G>T

Variant summary

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

The ENST00000505066.5(DDR1):​c.-43+2494G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.281 in 151,578 control chromosomes in the GnomAD database, including 6,867 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 (6867 hom., cov: 32)
• Consequence: DDR1 ENST00000505066.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.40
• Publications: 16 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=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.359 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+2494G>T		intron_variant	Intron 1 of 3	4		ENSP00000421189.1
DDR1	ENST00000502955.5	c.-270-1845G>T		intron_variant	Intron 1 of 3	4		ENSP00000424346.1

Frequencies

GnomAD3 genomes AF: 0.281 AC: 42617 AN: 151462 Hom.: 6869 Cov.: 32

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.310

Gnomad AMR AF: 0.246

Gnomad ASJ AF: 0.392

Gnomad EAS AF: 0.257

Gnomad SAS AF: 0.268

Gnomad FIN AF: 0.393

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.363

Gnomad OTH AF: 0.282

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

GnomAD4 genome AF: 0.281 AC: 42626 AN: 151578 Hom.: 6867 Cov.: 32 AF XY: 0.282 AC XY: 20923 AN XY: 74088

African (AFR) AF: 0.126 AC: 5183 AN: 41234

American (AMR) AF: 0.246 AC: 3748 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.392 AC: 1358 AN: 3460

East Asian (EAS) AF: 0.257 AC: 1324 AN: 5158

South Asian (SAS) AF: 0.267 AC: 1270 AN: 4764

European-Finnish (FIN) AF: 0.393 AC: 4131 AN: 10512

Middle Eastern (MID) AF: 0.378 AC: 111 AN: 294

European-Non Finnish (NFE) AF: 0.363 AC: 24631 AN: 67920

Other (OTH) AF: 0.279 AC: 588 AN: 2104

Alfa AF: 0.321 Hom.: 16743

Bravo AF: 0.263

Asia WGS AF: 0.212 AC: 743 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.0050
DANN	Benign	0.53
PhyloP100		-1.4

Splicing

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

Other links and lift over

dbSNP: rs1264331; hg19: chr6-30846830;