9-91725177-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004560.4(ROR2):c.1387-70G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.284 in 1,603,272 control chromosomes in the GnomAD database, including 66,805 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.25 (5472 hom., cov: 33)
  • Exomes 𝑓: 0.29 (61333 hom.)
• Consequence: ROR2 NM_004560.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.67

Genes affected

ROR2 (HGNC:10257): (receptor tyrosine kinase like orphan receptor 2) The protein encoded by this gene is a receptor protein tyrosine kinase and type I transmembrane protein that belongs to the ROR subfamily of cell surface receptors. The protein may be involved in the early formation of the chondrocytes and may be required for cartilage and growth plate development. Mutations in this gene can cause brachydactyly type B, a skeletal disorder characterized by hypoplasia/aplasia of distal phalanges and nails. In addition, mutations in this gene can cause the autosomal recessive form of Robinow syndrome, which is characterized by skeletal dysplasia with generalized limb bone shortening, segmental defects of the spine, brachydactyly, and a dysmorphic facial appearance. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 9-91725177-C-T is Benign according to our data. Variant chr9-91725177-C-T is described in ClinVar as [Benign]. Clinvar id is 1270146.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.355 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ROR2	NM_004560.4	c.1387-70G>A		intron_variant		ENST00000375708.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ROR2	ENST00000375708.4	c.1387-70G>A		intron_variant		1	NM_004560.4	P1
ROR2	ENST00000375715.5	c.967-70G>A		intron_variant		1
ROR2	ENST00000550066.5	n.1855-70G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.254 AC: 38682 AN: 152008 Hom.: 5470 Cov.: 33

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.272

Gnomad AMR AF: 0.314

Gnomad ASJ AF: 0.303

Gnomad EAS AF: 0.369

Gnomad SAS AF: 0.297

Gnomad FIN AF: 0.357

Gnomad MID AF: 0.293

Gnomad NFE AF: 0.284

Gnomad OTH AF: 0.273

GnomAD4 exome AF: 0.287 AC: 416838 AN: 1451146 Hom.: 61333 AF XY: 0.288 AC XY: 207707 AN XY: 722308

Gnomad4 AFR exome AF: 0.123

Gnomad4 AMR exome AF: 0.368

Gnomad4 ASJ exome AF: 0.302

Gnomad4 EAS exome AF: 0.356

Gnomad4 SAS exome AF: 0.301

Gnomad4 FIN exome AF: 0.352

Gnomad4 NFE exome AF: 0.283

Gnomad4 OTH exome AF: 0.282

GnomAD4 genome AF: 0.254 AC: 38673 AN: 152126 Hom.: 5472 Cov.: 33 AF XY: 0.260 AC XY: 19314 AN XY: 74370

Gnomad4 AFR AF: 0.132

Gnomad4 AMR AF: 0.314

Gnomad4 ASJ AF: 0.303

Gnomad4 EAS AF: 0.369

Gnomad4 SAS AF: 0.297

Gnomad4 FIN AF: 0.357

Gnomad4 NFE AF: 0.284

Gnomad4 OTH AF: 0.270

Alfa AF: 0.266 Hom.: 5303

Bravo AF: 0.248

Asia WGS AF: 0.303 AC: 1052 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 16, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	0.0030
Dann	Benign	0.82

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: rs10992065; hg19: chr9-94487459; COSMIC: COSV65216589;