6-30894646-C-T

Variant names:

• chr6-30894646-C-T
• rs1264319
• NM_001297654.2:c.1488C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001297654.2(DDR1):​c.1488C>T​(p.Ser496Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 1,607,382 control chromosomes in the GnomAD database, including 32,034 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 0.18 (2496 hom., cov: 31)
  • Exomes 𝑓: 0.20 (29538 hom.)
• Consequence: DDR1 NM_001297654.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.438
• Publications: 37 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0015641451).
• BP7: Synonymous conserved (PhyloP=0.438 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.197 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDR1	NM_001297654.2	c.1488C>T	p.Ser496Ser	synonymous_variant	Exon 11 of 18	ENST00000376568.8	NP_001284583.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDR1	ENST00000376568.8	c.1488C>T	p.Ser496Ser	synonymous_variant	Exon 11 of 18	1	NM_001297654.2	ENSP00000365752.3

Frequencies

GnomAD3 genomes AF: 0.175 AC: 26566 AN: 151970 Hom.: 2484 Cov.: 31

Gnomad AFR AF: 0.186

Gnomad AMI AF: 0.229

Gnomad AMR AF: 0.121

Gnomad ASJ AF: 0.136

Gnomad EAS AF: 0.0776

Gnomad SAS AF: 0.125

Gnomad FIN AF: 0.139

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.199

Gnomad OTH AF: 0.144

GnomAD2 exomes AF: 0.163 AC: 39707 AN: 244250 AF XY: 0.164

Gnomad AFR exome AF: 0.188

Gnomad AMR exome AF: 0.117

Gnomad ASJ exome AF: 0.146

Gnomad EAS exome AF: 0.0757

Gnomad FIN exome AF: 0.134

Gnomad NFE exome AF: 0.197

Gnomad OTH exome AF: 0.151

GnomAD4 exome AF: 0.196 AC: 285167 AN: 1455294 Hom.: 29538 Cov.: 33 AF XY: 0.195 AC XY: 140997 AN XY: 723884

African (AFR) AF: 0.194 AC: 6460 AN: 33274

American (AMR) AF: 0.117 AC: 5127 AN: 43956

Ashkenazi Jewish (ASJ) AF: 0.146 AC: 3753 AN: 25744

East Asian (EAS) AF: 0.0714 AC: 2811 AN: 39386

South Asian (SAS) AF: 0.145 AC: 12334 AN: 85270

European-Finnish (FIN) AF: 0.136 AC: 7223 AN: 53266

Middle Eastern (MID) AF: 0.117 AC: 670 AN: 5736

European-Non Finnish (NFE) AF: 0.213 AC: 235723 AN: 1108548

Other (OTH) AF: 0.184 AC: 11066 AN: 60114

GnomAD4 genome AF: 0.175 AC: 26620 AN: 152088 Hom.: 2496 Cov.: 31 AF XY: 0.170 AC XY: 12623 AN XY: 74354

African (AFR) AF: 0.186 AC: 7723 AN: 41442

American (AMR) AF: 0.121 AC: 1851 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.136 AC: 471 AN: 3466

East Asian (EAS) AF: 0.0778 AC: 403 AN: 5180

South Asian (SAS) AF: 0.126 AC: 609 AN: 4820

European-Finnish (FIN) AF: 0.139 AC: 1476 AN: 10606

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.199 AC: 13544 AN: 67954

Other (OTH) AF: 0.143 AC: 303 AN: 2114

Alfa AF: 0.186 Hom.: 11412

Bravo AF: 0.175

TwinsUK AF: 0.236 AC: 875

ALSPAC AF: 0.223 AC: 859

ESP6500AA AF: 0.195 AC: 858

ESP6500EA AF: 0.198 AC: 1699

ExAC AF: 0.165 AC: 19999

Asia WGS AF: 0.124 AC: 430 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.14
CADD	Benign	6.0
DANN	Benign	0.88
DEOGEN2	Benign	0.030	T;T
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.11
FATHMM_MKL	Benign	0.019	N
LIST_S2	Benign	0.0	.;.
MetaRNN	Benign	0.0016	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	.;.
PhyloP100		0.44
PROVEAN	Benign	0.0	.;N
REVEL	Benign	0.0
Sift	Pathogenic	0.0	.;T
Sift4G	Uncertain	0.045	D;T
Vest4		0.13
ClinPred		0.0034	T
GERP RS		2.7
PromoterAI		-0.0098	Neutral
Mutation Taster		=88/12	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: rs1264319; hg19: chr6-30862423; COSMIC: COSV61318550; COSMIC: COSV61318550;