6-30888778-A-G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_001297654.2(DDR1):c.49A>G(p.Ser17Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000563 in 1,612,890 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.0026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00036 (4 hom.)
• Consequence: DDR1 NM_001297654.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.148

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 Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.007289231).
• BP6: Variant 6-30888778-A-G is Benign according to our data. Variant chr6-30888778-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 731041.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DDR1	NM_001297654.2	c.49A>G	p.Ser17Gly	missense_variant	2/18	ENST00000376568.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DDR1	ENST00000376568.8	c.49A>G	p.Ser17Gly	missense_variant	2/18	1	NM_001297654.2	P1

Frequencies

GnomAD3 genomes AF: 0.00255 AC: 388 AN: 151992 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00836

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00144

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000177

Gnomad OTH AF: 0.00335

GnomAD3 exomes AF: 0.000702 AC: 173 AN: 246600 Hom.: 0 AF XY: 0.000432 AC XY: 58 AN XY: 134400

Gnomad AFR exome AF: 0.00755

Gnomad AMR exome AF: 0.00110

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000165

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000117

Gnomad OTH exome AF: 0.000494

GnomAD4 exome AF: 0.000355 AC: 519 AN: 1460780 Hom.: 4 Cov.: 31 AF XY: 0.000345 AC XY: 251 AN XY: 726706

Gnomad4 AFR exome AF: 0.00594

Gnomad4 AMR exome AF: 0.00132

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000162

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000168

Gnomad4 OTH exome AF: 0.000894

GnomAD4 genome AF: 0.00256 AC: 389 AN: 152110 Hom.: 0 Cov.: 32 AF XY: 0.00246 AC XY: 183 AN XY: 74366

Gnomad4 AFR AF: 0.00834

Gnomad4 AMR AF: 0.00144

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000177

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.000867 Hom.: 0

Bravo AF: 0.00288

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.00104 AC: 4

ESP6500AA AF: 0.00860 AC: 26

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000742 AC: 88

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jun 05, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.056
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Uncertain	-0.060
Cadd	Benign	15
Dann	Uncertain	0.98
Eigen	Benign	-0.94
Eigen_PC	Benign	-0.89
FATHMM_MKL	Benign	0.073	N
LIST_S2	Uncertain	0.89	D;D;D;.;D;.;D;.;D;D;D;D;D;.;.;D;D;.;D;D;D;.;.;D;D;.;.;.;D;.;D;D;D;D;.;.;.;D
MetaRNN	Benign	0.0073	T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Uncertain	0.23	D
MutationTaster	Benign	1.0	N;N;N;N;N;N;N;N;N;N;N;N
PrimateAI	Benign	0.46	T
PROVEAN	Uncertain	-2.5	D;N;N;N;N;D;N;N;N;N;N;N;N;N;N;N;N;N;N;D;N;N;N;N;N;N;N;N;N;N;N;N;N;D;N;N;N;N
REVEL	Uncertain	0.34
Sift	Benign	0.18	T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;D;T;T;T;T
Sift4G	Uncertain	0.027	D;T;T;T;T;D;T;T;T;D;T;D;T;T;T;D;T;T;T;D;T;T;T;T;T;T;T;T;T;T;T;T;T;D;T;T;D;T
Polyphen		0.0040, 0.15, 0.0050	.;.;.;B;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;B;B;.;.;.;.;.;.;.;.;.;B;B
Vest4		0.15, 0.14, 0.17, 0.14, 0.14, 0.15, 0.14, 0.094, 0.14
MVP		0.76
MPC		0.46
ClinPred		0.012	T
GERP RS		-0.81
Varity_R		0.034
gMVP		0.42

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs55901302; hg19: chr6-30856555; COSMIC: COSV104411224; COSMIC: COSV104411224;