chr1-162770537-T-C

Variant names:

• chr1-162770537-T-C
• rs1780003
• NM_006182.4:c.1504+25T>C

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_006182.4(DDR2):​c.1504+25T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.991 in 1,611,812 control chromosomes in the GnomAD database, including 793,088 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.96 (69714 hom., cov: 29)
  • Exomes 𝑓: 1.0 (723374 hom.)
• Consequence: DDR2 NM_006182.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts U:1 B:5
• Conservation: PhyloP100: -1.39
• Publications: 10 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 -16 ACMG points.

• BP6: Variant 1-162770537-T-C is Benign according to our data. Variant chr1-162770537-T-C is described in ClinVar as Benign. ClinVar VariationId is 259930.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.

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.1504+25T>C		intron	N/A	NP_006173.2	Q16832
	DDR2	NM_001014796.3		c.1504+25T>C		intron	N/A	NP_001014796.1	Q16832
	DDR2	NM_001354982.2		c.1504+25T>C		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.1504+25T>C		intron	N/A	ENSP00000356898.3	Q16832
	DDR2	ENST00000367922.7	TSL:1	c.1504+25T>C		intron	N/A	ENSP00000356899.2	Q16832
	DDR2	ENST00000877159.1		c.1529T>C	p.Val510Ala	missense	Exon 12 of 18	ENSP00000547218.1

Frequencies

GnomAD3 genomes AF: 0.955 AC: 145112 AN: 151904 Hom.: 69673 Cov.: 29

Gnomad AFR AF: 0.845

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.984

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.998

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.994

Gnomad NFE AF: 0.999

Gnomad OTH AF: 0.964

GnomAD2 exomes AF: 0.988 AC: 247517 AN: 250514 AF XY: 0.991

Gnomad AFR exome AF: 0.842

Gnomad AMR exome AF: 0.992

Gnomad ASJ exome AF: 1.00

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 1.00

Gnomad NFE exome AF: 0.999

Gnomad OTH exome AF: 0.992

GnomAD4 exome AF: 0.995 AC: 1452822 AN: 1459790 Hom.: 723374 Cov.: 35 AF XY: 0.996 AC XY: 723311 AN XY: 726314

African (AFR) AF: 0.840 AC: 28078 AN: 33416

American (AMR) AF: 0.990 AC: 44254 AN: 44688

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 26126 AN: 26126

East Asian (EAS) AF: 1.00 AC: 39643 AN: 39644

South Asian (SAS) AF: 0.999 AC: 86158 AN: 86208

European-Finnish (FIN) AF: 1.00 AC: 53392 AN: 53394

Middle Eastern (MID) AF: 0.989 AC: 5700 AN: 5762

European-Non Finnish (NFE) AF: 1.00 AC: 1109844 AN: 1110224

Other (OTH) AF: 0.988 AC: 59627 AN: 60328

GnomAD4 genome AF: 0.955 AC: 145213 AN: 152022 Hom.: 69714 Cov.: 29 AF XY: 0.956 AC XY: 71048 AN XY: 74284

African (AFR) AF: 0.845 AC: 34982 AN: 41416

American (AMR) AF: 0.984 AC: 15023 AN: 15274

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

East Asian (EAS) AF: 1.00 AC: 5132 AN: 5134

South Asian (SAS) AF: 0.999 AC: 4792 AN: 4796

European-Finnish (FIN) AF: 1.00 AC: 10604 AN: 10604

Middle Eastern (MID) AF: 0.993 AC: 292 AN: 294

European-Non Finnish (NFE) AF: 0.999 AC: 67972 AN: 68012

Other (OTH) AF: 0.964 AC: 2034 AN: 2110

Alfa AF: 0.982 Hom.: 201867

Bravo AF: 0.950

TwinsUK AF: 1.00 AC: 3707

ALSPAC AF: 1.00 AC: 3854

ESP6500AA AF: 0.847 AC: 3731

ESP6500EA AF: 0.999 AC: 8593

ExAC AF: 0.985 AC: 119584

Asia WGS AF: 0.992 AC: 3449 AN: 3478

EpiCase AF: 1.00

EpiControl AF: 0.999

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_addAF	Benign	-0.76	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	4.6
DANN	Benign	0.55
Eigen	Benign	-1.9
Eigen_PC	Benign	-2.2
FATHMM_MKL	Benign	0.019	N
LIST_S2	Benign	0.15	T
MetaRNN	Benign	0.0000011	T
MetaSVM	Benign	-1.1	T
PhyloP100		-1.4
PROVEAN	Benign	0.31	N
REVEL	Benign	0.0060
Sift	Pathogenic	0.0	D
Sift4G	Benign	1.0	T
ClinPred		0.016	T
GERP RS		-10
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.24		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.24		Position offset: 29

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

Other links and lift over

dbSNP: rs1780003; hg19: chr1-162740327;