rs1355287

Variant names:

• chr1-162773628-G-T
• rs1355287
• NM_006182.4:c.1856+32G>T

Your query was ambiguous. Multiple possible variants found:

• chr1-162773628-G-T
• chr1-162773628-G-C

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.1856+32G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.999 in 1,612,978 control chromosomes in the GnomAD database, including 805,221 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 1.0 (75527 hom., cov: 32)
  • Exomes 𝑓: 1.0 (729694 hom.)
• Consequence: DDR2 NM_006182.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts U:1 B:5
• Conservation: PhyloP100: 1.33
• 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 1-162773628-G-T is Benign according to our data. Variant chr1-162773628-G-T is described in ClinVar as Benign. ClinVar VariationId is 259932.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.994 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.1856+32G>T		intron	N/A	NP_006173.2	Q16832
	DDR2	NM_001014796.3		c.1856+32G>T		intron	N/A	NP_001014796.1	Q16832
	DDR2	NM_001354982.2		c.1856+32G>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.1856+32G>T		intron	N/A	ENSP00000356898.3	Q16832
	DDR2	ENST00000367922.7	TSL:1	c.1856+32G>T		intron	N/A	ENSP00000356899.2	Q16832
	DDR2	ENST00000877159.1		c.1910+32G>T		intron	N/A	ENSP00000547218.1

Frequencies

GnomAD3 genomes AF: 0.996 AC: 151583 AN: 152236 Hom.: 75468 Cov.: 32

Gnomad AFR AF: 0.985

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.999

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.999

Gnomad FIN AF: 1.00

Gnomad MID AF: 1.00

Gnomad NFE AF: 1.00

Gnomad OTH AF: 0.997

GnomAD2 exomes AF: 0.999 AC: 250863 AN: 251134 AF XY: 0.999

Gnomad AFR exome AF: 0.986

Gnomad AMR exome AF: 0.999

Gnomad ASJ exome AF: 1.00

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 1.00

Gnomad NFE exome AF: 1.00

Gnomad OTH exome AF: 0.999

GnomAD4 exome AF: 1.00 AC: 1460003 AN: 1460624 Hom.: 729694 Cov.: 51 AF XY: 1.00 AC XY: 726367 AN XY: 726646

African (AFR) AF: 0.986 AC: 32964 AN: 33434

American (AMR) AF: 0.999 AC: 44649 AN: 44684

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 26104 AN: 26104

East Asian (EAS) AF: 1.00 AC: 39662 AN: 39662

South Asian (SAS) AF: 1.00 AC: 86094 AN: 86124

European-Finnish (FIN) AF: 1.00 AC: 53304 AN: 53304

Middle Eastern (MID) AF: 0.999 AC: 5755 AN: 5758

European-Non Finnish (NFE) AF: 1.00 AC: 1111224 AN: 1111230

Other (OTH) AF: 0.999 AC: 60247 AN: 60324

GnomAD4 genome AF: 0.996 AC: 151701 AN: 152354 Hom.: 75527 Cov.: 32 AF XY: 0.996 AC XY: 74176 AN XY: 74494

African (AFR) AF: 0.985 AC: 40949 AN: 41574

American (AMR) AF: 0.999 AC: 15290 AN: 15306

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3472 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5186 AN: 5186

South Asian (SAS) AF: 0.999 AC: 4822 AN: 4826

European-Finnish (FIN) AF: 1.00 AC: 10628 AN: 10628

Middle Eastern (MID) AF: 1.00 AC: 294 AN: 294

European-Non Finnish (NFE) AF: 1.00 AC: 68040 AN: 68042

Other (OTH) AF: 0.997 AC: 2110 AN: 2116

Alfa AF: 0.999 Hom.: 8768

Bravo AF: 0.995

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)
-	-	1	Spondyloepimetaphyseal dysplasia-short limb-abnormal calcification syndrome (1)
-	1	-	Squamous cell lung carcinoma (1)
-	-	1	Warburg-cinotti syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	15
DANN	Benign	0.59
PhyloP100		1.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.20		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.20		Position offset: 16

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

Other links and lift over

dbSNP: rs1355287; hg19: chr1-162743418;