chr6-30888935-A-G

Position:

• chr6-30888935-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001297654.2(DDR1):​c.113A>G​(p.Gln38Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,766 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: DDR1 NM_001297654.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.33

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DDR1	NM_001297654.2	c.113A>G	p.Gln38Arg	missense_variant	3/18	ENST00000376568.8	NP_001284583.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DDR1	ENST00000376568.8	c.113A>G	p.Gln38Arg	missense_variant	3/18	1	NM_001297654.2	ENSP00000365752.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460766 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726698

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 01, 2024

The c.113A>G (p.Q38R) alteration is located in exon 2 (coding exon 2) of the DDR1 gene. This alteration results from a A to G substitution at nucleotide position 113, causing the glutamine (Q) at amino acid position 38 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Uncertain	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	.;T;T;T;.;T;.;.;T;.;T;.;T;.;T;T;.;T;.;T;T;.;.;T;T;T;T;.;T;T;T;T;.;.;.;T;.;.
Eigen	Benign	0.16
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.87	D;D;D;.;D;.;D;.;D;D;D;D;D;.;.;D;D;.;D;D;D;.;.;D;D;.;.;.;D;.;D;D;D;D;.;.;.;D
M_CAP	Pathogenic	0.50	D
MetaRNN	Uncertain	0.47	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	Pathogenic	1.0	D
MutationAssessor	Benign	1.8	.;.;.;L;.;.;.;L;.;.;.;.;.;L;.;.;.;.;.;.;.;L;L;.;.;L;L;.;.;.;.;.;.;.;L;.;L;L
PrimateAI	Uncertain	0.61	T
PROVEAN	Uncertain	-2.6	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	0.49
Sift	Uncertain	0.0020	D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
Sift4G	Pathogenic	0.0	D;D;D;D;D;D;D;D;D;D;T;D;D;D;D;D;D;D;T;D;D;D;D;D;D;D;D;D;D;T;D;D;D;D;D;D;T;D
Polyphen		0.69, 0.76, 0.61	.;.;.;P;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;P;P;.;.;.;.;.;.;.;.;.;P;P
Vest4		0.31, 0.36, 0.35, 0.33, 0.31, 0.33, 0.29, 0.29, 0.40, 0.30
MutPred		0.14		Gain of disorder (P = 0.0699);Gain of disorder (P = 0.0699);Gain of disorder (P = 0.0699);Gain of disorder (P = 0.0699);Gain of disorder (P = 0.0699);Gain of disorder (P = 0.0699);Gain of disorder (P = 0.0699);Gain of disorder (P = 0.0699);Gain of disorder (P = 0.0699);Gain of disorder (P = 0.0699);Gain of disorder (P = 0.0699);Gain of disorder (P = 0.0699);Gain of disorder (P = 0.0699);Gain of disorder (P = 0.0699);Gain of disorder (P = 0.0699);Gain of disorder (P = 0.0699);Gain of disorder (P = 0.0699);Gain of disorder (P = 0.0699);Gain of disorder (P = 0.0699);Gain of disorder (P = 0.0699);Gain of disorder (P = 0.0699);Gain of disorder (P = 0.0699);Gain of disorder (P = 0.0699);Gain of disorder (P = 0.0699);Gain of disorder (P = 0.0699);Gain of disorder (P = 0.0699);Gain of disorder (P = 0.0699);.;Gain of disorder (P = 0.0699);Gain of disorder (P = 0.0699);Gain of disorder (P = 0.0699);Gain of disorder (P = 0.0699);.;Gain of disorder (P = 0.0699);Gain of disorder (P = 0.0699);Gain of disorder (P = 0.0699);Gain of disorder (P = 0.0699);Gain of disorder (P = 0.0699);
MVP		0.93
MPC		1.0
ClinPred		0.93	D
GERP RS		5.2
Varity_R		0.46
gMVP		0.70

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-30856712;