chr1-162679681-C-T

Position:

• chr1-162679681-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000367921.8(DDR2):​c.-28+24307C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.696 in 152,058 control chromosomes in the GnomAD database, including 37,908 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.70 (37908 hom., cov: 31)
• Consequence: DDR2 ENST00000367921.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.22

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.772 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DDR2	NM_006182.4	c.-28+24307C>T		intron_variant		ENST00000367921.8	NP_006173.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DDR2	ENST00000367921.8	c.-28+24307C>T		intron_variant		1	NM_006182.4	ENSP00000356898	P1

Frequencies

GnomAD3 genomes AF: 0.696 AC: 105798 AN: 151940 Hom.: 37908 Cov.: 31

Gnomad AFR AF: 0.529

Gnomad AMI AF: 0.681

Gnomad AMR AF: 0.613

Gnomad ASJ AF: 0.874

Gnomad EAS AF: 0.742

Gnomad SAS AF: 0.767

Gnomad FIN AF: 0.829

Gnomad MID AF: 0.823

Gnomad NFE AF: 0.778

Gnomad OTH AF: 0.708

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.696 AC: 105834 AN: 152058 Hom.: 37908 Cov.: 31 AF XY: 0.698 AC XY: 51890 AN XY: 74332

Gnomad4 AFR AF: 0.528

Gnomad4 AMR AF: 0.613

Gnomad4 ASJ AF: 0.874

Gnomad4 EAS AF: 0.743

Gnomad4 SAS AF: 0.767

Gnomad4 FIN AF: 0.829

Gnomad4 NFE AF: 0.778

Gnomad4 OTH AF: 0.710

Alfa AF: 0.732 Hom.: 4913

Bravo AF: 0.671

Asia WGS AF: 0.727 AC: 2531 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.76
DANN	Benign	0.40

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: rs7521233; hg19: chr1-162649471;