1-162753056-C-G

Variant names:

• chr1-162753056-C-G
• rs1632311
• NM_006182.4:c.83-39C>G

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.83-39C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.995 in 1,552,036 control chromosomes in the GnomAD database, including 769,298 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.98 (72691 hom., cov: 31)
  • Exomes 𝑓: 1.0 (696607 hom.)
• Consequence: DDR2 NM_006182.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.0130
• Publications: 5 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: Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae), G2P, Orphanet
• warburg-cinotti syndrome

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 1-162753056-C-G is Benign according to our data. Variant chr1-162753056-C-G is described in ClinVar as Benign. ClinVar VariationId is 259936.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDR2	NM_006182.4	c.83-39C>G		intron_variant	Intron 3 of 17	ENST00000367921.8	NP_006173.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDR2	ENST00000367921.8	c.83-39C>G		intron_variant	Intron 3 of 17	1	NM_006182.4	ENSP00000356898.3

Frequencies

GnomAD3 genomes AF: 0.976 AC: 148567 AN: 152150 Hom.: 72646 Cov.: 31

Gnomad AFR AF: 0.918

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.992

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.997

Gnomad NFE AF: 1.00

Gnomad OTH AF: 0.982

GnomAD2 exomes AF: 0.994 AC: 249039 AN: 250582 AF XY: 0.995

Gnomad AFR exome AF: 0.915

Gnomad AMR exome AF: 0.996

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: 0.997

GnomAD4 exome AF: 0.998 AC: 1396365 AN: 1399768 Hom.: 696607 Cov.: 20 AF XY: 0.998 AC XY: 698573 AN XY: 700050

African (AFR) AF: 0.914 AC: 29410 AN: 32164

American (AMR) AF: 0.996 AC: 44269 AN: 44462

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 25590 AN: 25590

East Asian (EAS) AF: 1.00 AC: 39262 AN: 39264

South Asian (SAS) AF: 1.00 AC: 84737 AN: 84758

European-Finnish (FIN) AF: 1.00 AC: 52840 AN: 52840

Middle Eastern (MID) AF: 0.996 AC: 5291 AN: 5310

European-Non Finnish (NFE) AF: 1.00 AC: 1057185 AN: 1057300

Other (OTH) AF: 0.995 AC: 57781 AN: 58080

GnomAD4 genome AF: 0.976 AC: 148670 AN: 152268 Hom.: 72691 Cov.: 31 AF XY: 0.977 AC XY: 72725 AN XY: 74434

African (AFR) AF: 0.918 AC: 38112 AN: 41526

American (AMR) AF: 0.992 AC: 15169 AN: 15294

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

East Asian (EAS) AF: 1.00 AC: 5168 AN: 5168

South Asian (SAS) AF: 1.00 AC: 4821 AN: 4822

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

Middle Eastern (MID) AF: 0.997 AC: 293 AN: 294

European-Non Finnish (NFE) AF: 1.00 AC: 68016 AN: 68036

Other (OTH) AF: 0.983 AC: 2079 AN: 2116

Alfa AF: 0.989 Hom.: 13677

Bravo AF: 0.973

Asia WGS AF: 0.998 AC: 3471 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Apr 12, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Warburg-cinotti syndrome Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Spondyloepimetaphyseal dysplasia-short limb-abnormal calcification syndrome Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	3.2
DANN	Benign	0.69
PhyloP100		-0.013
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: rs1632311; hg19: chr1-162722846;