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

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]

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 id 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

Gnomad4 AFR exome AF: 0.914 AC: 29410 AN: 32164

Gnomad4 AMR exome AF: 0.996 AC: 44269 AN: 44462

Gnomad4 ASJ exome AF: 1.00 AC: 25590 AN: 25590

Gnomad4 EAS exome AF: 1.00 AC: 39262 AN: 39264

Gnomad4 SAS exome AF: 1.00 AC: 84737 AN: 84758

Gnomad4 FIN exome AF: 1.00 AC: 52840 AN: 52840

Gnomad4 NFE exome AF: 1.00 AC: 1057185 AN: 1057300

Gnomad4 Remaining exome 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

Gnomad4 AFR AF: 0.918 AC: 0.917786 AN: 0.917786

Gnomad4 AMR AF: 0.992 AC: 0.991827 AN: 0.991827

Gnomad4 ASJ AF: 1.00 AC: 1 AN: 1

Gnomad4 EAS AF: 1.00 AC: 1 AN: 1

Gnomad4 SAS AF: 1.00 AC: 0.999793 AN: 0.999793

Gnomad4 FIN AF: 1.00 AC: 1 AN: 1

Gnomad4 NFE AF: 1.00 AC: 0.999706 AN: 0.999706

Gnomad4 OTH AF: 0.983 AC: 0.982514 AN: 0.982514

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

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Apr 12, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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
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

Publications

LitVar

Other links and lift over

dbSNP: rs1632311; hg19: chr1-162722846;