rs147441352

Positions:

• chr9-91726782-T-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_004560.4(ROR2):​c.1184-39A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00163 in 1,598,732 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0011 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0017 (5 hom.)
• Consequence: ROR2 NM_004560.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.20

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 9-91726782-T-A is Benign according to our data. Variant chr9-91726782-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 259429.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ROR2	NM_004560.4	c.1184-39A>T		intron_variant		ENST00000375708.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ROR2	ENST00000375708.4	c.1184-39A>T		intron_variant		1	NM_004560.4	P1
ROR2	ENST00000375715.5	c.764-39A>T		intron_variant		1
ROR2	ENST00000550066.5	n.1652-39A>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.00111 AC: 169 AN: 152104 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000362

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.000289

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00353

Gnomad FIN AF: 0.00377

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00135

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.00139 AC: 343 AN: 247606 Hom.: 1 AF XY: 0.00166 AC XY: 223 AN XY: 134388

Gnomad AFR exome AF: 0.000190

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00304

Gnomad FIN exome AF: 0.00350

Gnomad NFE exome AF: 0.00149

Gnomad OTH exome AF: 0.000495

GnomAD4 exome AF: 0.00168 AC: 2431 AN: 1446510 Hom.: 5 Cov.: 28 AF XY: 0.00176 AC XY: 1270 AN XY: 720516

Gnomad4 AFR exome AF: 0.000121

Gnomad4 AMR exome AF: 0.0000896

Gnomad4 ASJ exome AF: 0.000115

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00344

Gnomad4 FIN exome AF: 0.00288

Gnomad4 NFE exome AF: 0.00174

Gnomad4 OTH exome AF: 0.00105

GnomAD4 genome AF: 0.00112 AC: 170 AN: 152222 Hom.: 1 Cov.: 32 AF XY: 0.00121 AC XY: 90 AN XY: 74424

Gnomad4 AFR AF: 0.000361

Gnomad4 AMR AF: 0.000196

Gnomad4 ASJ AF: 0.000289

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00374

Gnomad4 FIN AF: 0.00377

Gnomad4 NFE AF: 0.00135

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.000825 Hom.: 0

Bravo AF: 0.000733

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.037
DANN	Benign	0.67

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: rs147441352; hg19: chr9-94489064;