1-162772004-C-T

Variant names:

• chr1-162772004-C-T
• rs3738807
• NM_006182.4:c.1505-20C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006182.4(DDR2):​c.1505-20C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0648 in 1,580,484 control chromosomes in the GnomAD database, including 5,334 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.061 (587 hom., cov: 32)
  • Exomes 𝑓: 0.065 (4747 hom.)
• Consequence: DDR2 NM_006182.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -2.42
• Publications: 8 publications found

Genes affected

DDR2 (HGNC:2731): (discoidin domain receptor tyrosine kinase 2) This gene encodes a member of the discoidin domain receptor subclass of the receptor tyrosine kinase (RTKs) protein family. RTKs play a key role in the communication of cells with their microenvironment. The encoded protein is a collagen-induced receptor that activates signal transduction pathways involved in cell adhesion, proliferation, and extracellular matrix remodeling. This protein is expressed in numerous cell types and may alos be involved in wound repair and regulate tumor growth and invasiveness. Mutations in this gene are the cause of short limb-hand type spondylometaepiphyseal dysplasia. [provided by RefSeq, Aug 2017]

DDR2 Gene-Disease associations (from GenCC):

• spondyloepimetaphyseal dysplasia-short limb-abnormal calcification syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: ClinGen, Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), Orphanet
• warburg-cinotti syndrome

  Inheritance: AD, Unknown Classification: STRONG, MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P, ClinGen, Illumina

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 1-162772004-C-T is Benign according to our data. Variant chr1-162772004-C-T is described in ClinVar as Benign. ClinVar VariationId is 259931.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.22 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006182.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDR2	NM_006182.4	MANE Select	c.1505-20C>T		intron	N/A	NP_006173.2	Q16832
	DDR2	NM_001014796.3		c.1505-20C>T		intron	N/A	NP_001014796.1	Q16832
	DDR2	NM_001354982.2		c.1505-20C>T		intron	N/A	NP_001341911.1	Q16832

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDR2	ENST00000367921.8	TSL:1 MANE Select	c.1505-20C>T		intron	N/A	ENSP00000356898.3	Q16832
	DDR2	ENST00000367922.7	TSL:1	c.1505-20C>T		intron	N/A	ENSP00000356899.2	Q16832
	DDR2	ENST00000877159.1		c.1559-20C>T		intron	N/A	ENSP00000547218.1

Frequencies

GnomAD3 genomes AF: 0.0606 AC: 9219 AN: 152146 Hom.: 587 Cov.: 32

Gnomad AFR AF: 0.0134

Gnomad AMI AF: 0.0768

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.0302

Gnomad EAS AF: 0.231

Gnomad SAS AF: 0.0871

Gnomad FIN AF: 0.0367

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0519

Gnomad OTH AF: 0.0727

GnomAD2 exomes AF: 0.0936 AC: 18726 AN: 200086 AF XY: 0.0858

Gnomad AFR exome AF: 0.0121

Gnomad AMR exome AF: 0.270

Gnomad ASJ exome AF: 0.0307

Gnomad EAS exome AF: 0.216

Gnomad FIN exome AF: 0.0345

Gnomad NFE exome AF: 0.0508

Gnomad OTH exome AF: 0.0764

GnomAD4 exome AF: 0.0653 AC: 93236 AN: 1428220 Hom.: 4747 Cov.: 31 AF XY: 0.0646 AC XY: 45744 AN XY: 707696

African (AFR) AF: 0.0114 AC: 372 AN: 32720

American (AMR) AF: 0.259 AC: 10223 AN: 39488

Ashkenazi Jewish (ASJ) AF: 0.0331 AC: 845 AN: 25494

East Asian (EAS) AF: 0.228 AC: 8626 AN: 37794

South Asian (SAS) AF: 0.0791 AC: 6495 AN: 82130

European-Finnish (FIN) AF: 0.0375 AC: 1936 AN: 51646

Middle Eastern (MID) AF: 0.0487 AC: 220 AN: 4516

European-Non Finnish (NFE) AF: 0.0554 AC: 60705 AN: 1095322

Other (OTH) AF: 0.0645 AC: 3814 AN: 59110

GnomAD4 genome AF: 0.0606 AC: 9227 AN: 152264 Hom.: 587 Cov.: 32 AF XY: 0.0641 AC XY: 4770 AN XY: 74458

African (AFR) AF: 0.0134 AC: 557 AN: 41566

American (AMR) AF: 0.183 AC: 2805 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0302 AC: 105 AN: 3472

East Asian (EAS) AF: 0.231 AC: 1189 AN: 5158

South Asian (SAS) AF: 0.0874 AC: 422 AN: 4828

European-Finnish (FIN) AF: 0.0367 AC: 389 AN: 10608

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0519 AC: 3529 AN: 68018

Other (OTH) AF: 0.0724 AC: 153 AN: 2114

Alfa AF: 0.0465 Hom.: 54

Bravo AF: 0.0719

Asia WGS AF: 0.150 AC: 521 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.024
DANN	Benign	0.46
PhyloP100		-2.4
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: rs3738807; hg19: chr1-162741794; COSMIC: COSV63369574;