chr1-162752966-A-G

Variant names:

• chr1-162752966-A-G
• rs191037278
• NM_006182.4:c.83-129A>G

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.83-129A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00535 in 779,086 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0044 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0056 (22 hom.)
• Consequence: DDR2 NM_006182.4 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0890
• 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: 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=-0.81).
• BP6: Variant 1-162752966-A-G is Benign according to our data. Variant chr1-162752966-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 1202066.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00444 (677/152362) while in subpopulation AMR AF = 0.00588 (90/15306). AF 95% confidence interval is 0.00519. There are 4 homozygotes in GnomAd4. There are 337 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 4 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.83-129A>G		intron	N/A	NP_006173.2	Q16832
	DDR2	NM_001014796.3		c.83-129A>G		intron	N/A	NP_001014796.1	Q16832
	DDR2	NM_001354982.2		c.83-129A>G		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.83-129A>G		intron	N/A	ENSP00000356898.3	Q16832
	DDR2	ENST00000367922.7	TSL:1	c.83-129A>G		intron	N/A	ENSP00000356899.2	Q16832
	DDR2	ENST00000877159.1		c.83-129A>G		intron	N/A	ENSP00000547218.1

Frequencies

GnomAD3 genomes AF: 0.00446 AC: 679 AN: 152244 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.00145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00589

Gnomad ASJ AF: 0.00490

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.0102

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00569

Gnomad OTH AF: 0.00430

GnomAD4 exome AF: 0.00558 AC: 3494 AN: 626724 Hom.: 22 AF XY: 0.00532 AC XY: 1768 AN XY: 332354

African (AFR) AF: 0.00212 AC: 35 AN: 16530

American (AMR) AF: 0.00438 AC: 142 AN: 32394

Ashkenazi Jewish (ASJ) AF: 0.00623 AC: 114 AN: 18310

East Asian (EAS) AF: 0.00 AC: 0 AN: 27828

South Asian (SAS) AF: 0.00126 AC: 80 AN: 63610

European-Finnish (FIN) AF: 0.0147 AC: 521 AN: 35412

Middle Eastern (MID) AF: 0.00255 AC: 6 AN: 2356

European-Non Finnish (NFE) AF: 0.00602 AC: 2410 AN: 400090

Other (OTH) AF: 0.00616 AC: 186 AN: 30194

GnomAD4 genome AF: 0.00444 AC: 677 AN: 152362 Hom.: 4 Cov.: 32 AF XY: 0.00452 AC XY: 337 AN XY: 74510

African (AFR) AF: 0.00144 AC: 60 AN: 41590

American (AMR) AF: 0.00588 AC: 90 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00490 AC: 17 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5176

South Asian (SAS) AF: 0.00124 AC: 6 AN: 4832

European-Finnish (FIN) AF: 0.0102 AC: 108 AN: 10626

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00566 AC: 385 AN: 68042

Other (OTH) AF: 0.00426 AC: 9 AN: 2114

Alfa AF: 0.00455 Hom.: 0

Bravo AF: 0.00402

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

ClinVar submissions

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	-0.81
CADD	Benign	0.80
DANN	Benign	0.67
PhyloP100		-0.089
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: rs191037278; hg19: chr1-162722756;