rs1049623

Variant names:

• chr6-30897052-T-C
• rs1049623
• NM_001297654.2:c.1908T>C

Your query was ambiguous. Multiple possible variants found:

• chr6-30897052-T-C
• chr6-30897052-T-G

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_001297654.2(DDR1):​c.1908T>C​(p.Val636Val) 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
• Publications: 46 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 -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 rank	MANE	Protein	UniProt
DDR1	NM_001297654.2	c.1908T>C	p.Val636Val	synonymous_variant	Exon 14 of 18	ENST00000376568.8	NP_001284583.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDR1	ENST00000376568.8	c.1908T>C	p.Val636Val	synonymous_variant	Exon 14 of 18	1	NM_001297654.2	ENSP00000365752.3

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

GnomAD2 exomes AF: 0.469 AC: 117984 AN: 251318 AF XY: 0.469

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 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

African (AFR) AF: 0.454 AC: 15183 AN: 33474

American (AMR) AF: 0.581 AC: 25953 AN: 44684

Ashkenazi Jewish (ASJ) AF: 0.419 AC: 10957 AN: 26126

East Asian (EAS) AF: 0.647 AC: 25694 AN: 39686

South Asian (SAS) AF: 0.615 AC: 53067 AN: 86238

European-Finnish (FIN) AF: 0.395 AC: 21087 AN: 53408

Middle Eastern (MID) AF: 0.392 AC: 2260 AN: 5766

European-Non Finnish (NFE) AF: 0.388 AC: 431252 AN: 1111784

Other (OTH) AF: 0.447 AC: 26984 AN: 60388

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

African (AFR) AF: 0.458 AC: 18913 AN: 41330

American (AMR) AF: 0.489 AC: 7461 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.401 AC: 1394 AN: 3472

East Asian (EAS) AF: 0.683 AC: 3494 AN: 5116

South Asian (SAS) AF: 0.638 AC: 3035 AN: 4760

European-Finnish (FIN) AF: 0.396 AC: 4162 AN: 10516

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.385 AC: 26141 AN: 67894

Other (OTH) AF: 0.408 AC: 856 AN: 2096

Alfa AF: 0.407 Hom.: 37705

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
PhyloP100		0.58
PromoterAI		0.014	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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