9-91723486-GCTCT-G

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_004560.4(ROR2):c.*172_*175del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.425 in 1,056,250 control chromosomes in the GnomAD database, including 95,333 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.41 (12960 hom., cov: 0)
  • Exomes 𝑓: 0.43 (82373 hom.)
• Consequence: ROR2 NM_004560.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.383

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 -16 ACMG points.

• BP6: Variant 9-91723486-GCTCT-G is Benign according to our data. Variant chr9-91723486-GCTCT-G is described in ClinVar as [Benign]. Clinvar id is 367493.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.478 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ROR2	NM_004560.4	c.*172_*175del		3_prime_UTR_variant	9/9	ENST00000375708.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ROR2	ENST00000375708.4	c.*172_*175del		3_prime_UTR_variant	9/9	1	NM_004560.4	P1
ROR2	ENST00000375715.5	c.1920+664_1920+667del		intron_variant		1
ROR2	ENST00000550066.5	n.3472_3475del		non_coding_transcript_exon_variant	11/11	2

Frequencies

GnomAD3 genomes AF: 0.411 AC: 62253 AN: 151520 Hom.: 12962 Cov.: 0

Gnomad AFR AF: 0.348

Gnomad AMI AF: 0.396

Gnomad AMR AF: 0.487

Gnomad ASJ AF: 0.377

Gnomad EAS AF: 0.422

Gnomad SAS AF: 0.302

Gnomad FIN AF: 0.442

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.437

Gnomad OTH AF: 0.399

GnomAD4 exome AF: 0.427 AC: 386419 AN: 904612 Hom.: 82373 AF XY: 0.423 AC XY: 192723 AN XY: 455774

Gnomad4 AFR exome AF: 0.351

Gnomad4 AMR exome AF: 0.540

Gnomad4 ASJ exome AF: 0.377

Gnomad4 EAS exome AF: 0.448

Gnomad4 SAS exome AF: 0.318

Gnomad4 FIN exome AF: 0.440

Gnomad4 NFE exome AF: 0.436

Gnomad4 OTH exome AF: 0.412

GnomAD4 genome AF: 0.411 AC: 62256 AN: 151638 Hom.: 12960 Cov.: 0 AF XY: 0.410 AC XY: 30393 AN XY: 74080

Gnomad4 AFR AF: 0.347

Gnomad4 AMR AF: 0.487

Gnomad4 ASJ AF: 0.377

Gnomad4 EAS AF: 0.422

Gnomad4 SAS AF: 0.301

Gnomad4 FIN AF: 0.442

Gnomad4 NFE AF: 0.437

Gnomad4 OTH AF: 0.395

Alfa AF: 0.427 Hom.: 1728

Bravo AF: 0.415

Asia WGS AF: 0.339 AC: 1178 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Autosomal dominant Robinow syndrome 1 Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 16, 2018

- -

Brachydactyly Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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: rs140581955; hg19: chr9-94485768;