chr1-162718891-G-A

Variant names:

• chr1-162718891-G-A
• rs16843907
• NM_006182.4:c.-27-146G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_006182.4(DDR2):​c.-27-146G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00504 in 737,654 control chromosomes in the GnomAD database, including 62 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0077 (19 hom., cov: 32)
  • Exomes 𝑓: 0.0044 (43 hom.)
• Consequence: DDR2 NM_006182.4 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.36
• Publications: 0 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: Orphanet, Ambry Genetics, G2P, ClinGen, Labcorp Genetics (formerly Invitae)
• warburg-cinotti syndrome

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 1-162718891-G-A is Benign according to our data. Variant chr1-162718891-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1219420.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00766 (1166/152296) while in subpopulation EAS AF = 0.0347 (180/5186). AF 95% confidence interval is 0.0306. There are 19 homozygotes in GnomAd4. There are 557 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 19 Unknown,AR,AD gene

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.-27-146G>A		intron	N/A	NP_006173.2	Q16832
	DDR2	NM_001014796.3		c.-27-146G>A		intron	N/A	NP_001014796.1	Q16832
	DDR2	NM_001354982.2		c.-27-146G>A		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.-27-146G>A		intron	N/A	ENSP00000356898.3	Q16832
	DDR2	ENST00000367922.7	TSL:1	c.-27-146G>A		intron	N/A	ENSP00000356899.2	Q16832
	DDR2	ENST00000877159.1		c.-27-146G>A		intron	N/A	ENSP00000547218.1

Frequencies

GnomAD3 genomes AF: 0.00761 AC: 1158 AN: 152178 Hom.: 18 Cov.: 32

Gnomad AFR AF: 0.0210

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00242

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0346

Gnomad SAS AF: 0.00600

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000265

Gnomad OTH AF: 0.0115

GnomAD4 exome AF: 0.00436 AC: 2555 AN: 585358 Hom.: 43 AF XY: 0.00433 AC XY: 1340 AN XY: 309306

African (AFR) AF: 0.0220 AC: 355 AN: 16138

American (AMR) AF: 0.00135 AC: 44 AN: 32538

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17930

East Asian (EAS) AF: 0.0499 AC: 1560 AN: 31234

South Asian (SAS) AF: 0.00584 AC: 335 AN: 57362

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33450

Middle Eastern (MID) AF: 0.00374 AC: 10 AN: 2672

European-Non Finnish (NFE) AF: 0.000127 AC: 46 AN: 363426

Other (OTH) AF: 0.00670 AC: 205 AN: 30608

GnomAD4 genome AF: 0.00766 AC: 1166 AN: 152296 Hom.: 19 Cov.: 32 AF XY: 0.00748 AC XY: 557 AN XY: 74468

African (AFR) AF: 0.0210 AC: 874 AN: 41564

American (AMR) AF: 0.00242 AC: 37 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.0347 AC: 180 AN: 5186

South Asian (SAS) AF: 0.00600 AC: 29 AN: 4832

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000265 AC: 18 AN: 68014

Other (OTH) AF: 0.0128 AC: 27 AN: 2116

Alfa AF: 0.00763 Hom.: 2

Bravo AF: 0.00861

Asia WGS AF: 0.0370 AC: 128 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.0060
DANN	Benign	0.71
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism

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: rs16843907; hg19: chr1-162688681;