rs1049623

chr6-30897052-T-Cchr6-30897052-T-G

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_001297654.2(DDR1):c.1908T>C(p.Val636=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.421 in 1,613,196 control chromosomes in the GnomAD database, including 148,378 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 0.44 (14867 hom., cov: 29)
  • Exomes 𝑓: 0.42 (133511 hom.)
• Consequence: DDR1 NM_001297654.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.582

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]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP7: Synonymous conserved (PhyloP=0.582 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.664 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DDR1	NM_001297654.2	c.1908T>C	p.Val636=	synonymous_variant	14/18	ENST00000376568.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DDR1	ENST00000376568.8	c.1908T>C	p.Val636=	synonymous_variant	14/18	1	NM_001297654.2	P1

Frequencies

GnomAD3 genomes AF: 0.435 AC: 65938 AN: 151524 Hom.: 14830 Cov.: 29

Gnomad AFR AF: 0.457

Gnomad AMI AF: 0.525

Gnomad AMR AF: 0.489

Gnomad ASJ AF: 0.401

Gnomad EAS AF: 0.682

Gnomad SAS AF: 0.637

Gnomad FIN AF: 0.396

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.385

Gnomad OTH AF: 0.402

GnomAD3 exomes AF: 0.469 AC: 117984 AN: 251318 Hom.: 29541 AF XY: 0.469 AC XY: 63764 AN XY: 135814

Gnomad AFR exome AF: 0.458

Gnomad AMR exome AF: 0.593

Gnomad ASJ exome AF: 0.413

Gnomad EAS exome AF: 0.658

Gnomad SAS exome AF: 0.620

Gnomad FIN exome AF: 0.389

Gnomad NFE exome AF: 0.385

Gnomad OTH exome AF: 0.418

GnomAD4 exome AF: 0.419 AC: 612437 AN: 1461554 Hom.: 133511 Cov.: 53 AF XY: 0.424 AC XY: 308397 AN XY: 727058

Gnomad4 AFR exome AF: 0.454

Gnomad4 AMR exome AF: 0.581

Gnomad4 ASJ exome AF: 0.419

Gnomad4 EAS exome AF: 0.647

Gnomad4 SAS exome AF: 0.615

Gnomad4 FIN exome AF: 0.395

Gnomad4 NFE exome AF: 0.388

Gnomad4 OTH exome AF: 0.447

GnomAD4 genome AF: 0.435 AC: 66028 AN: 151642 Hom.: 14867 Cov.: 29 AF XY: 0.441 AC XY: 32635 AN XY: 74078

Gnomad4 AFR AF: 0.458

Gnomad4 AMR AF: 0.489

Gnomad4 ASJ AF: 0.401

Gnomad4 EAS AF: 0.683

Gnomad4 SAS AF: 0.638

Gnomad4 FIN AF: 0.396

Gnomad4 NFE AF: 0.385

Gnomad4 OTH AF: 0.408

Alfa AF: 0.401 Hom.: 24585

Bravo AF: 0.441

Asia WGS AF: 0.670 AC: 2328 AN: 3478

EpiCase AF: 0.385

EpiControl AF: 0.385

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
Cadd	Benign	10
Dann	Benign	0.82
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

LitVar

Other links and lift over

dbSNP: rs1049623; hg19: chr6-30864829; COSMIC: COSV61318564; COSMIC: COSV61318564;