Variant rs12683181 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004560.4(ROR2):c.494+25G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.714 in 1,609,944 control chromosomes in the GnomAD database, including 413,421 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.68 ( 35975 hom., cov: 33)

Exomes 𝑓: 0.72 ( 377446 hom. )

Consequence

ROR2
NM_004560.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.451

Variant links:

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]

ROR2 links:

ROR2 (HGNC:):

ROR2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 9-91756046-C-T is Benign according to our data. Variant chr9-91756046-C-T is described in ClinVar as [Benign]. Clinvar id is 259431.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.733 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ROR2	NM_004560.4 linkuse as main transcript	c.494+25G>A		intron_variant		ENST00000375708.4	NP_004551.2	Q01974

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ROR2	ENST00000375708.4 linkuse as main transcript	c.494+25G>A	intron_variant		1	NM_004560.4	ENSP00000364860.3	Q01974
ROR2	ENST00000375715.5 linkuse as main transcript	c.74+25G>A	intron_variant		1		ENSP00000364867.1	B1APY4
ROR2	ENST00000548585.2 linkuse as main transcript	n.228G>A	non_coding_transcript_exon_variant	3/3	5
ROR2	ENST00000550066.5 linkuse as main transcript	n.962+25G>A	intron_variant		2

Frequencies

GnomAD3 genomes

AF:

0.684

AC:

104039

AN:

152030

Hom.:

35952

Cov.:

show subpopulations

Gnomad AFR

AF:

0.641

Gnomad AMI

AF:

0.704

Gnomad AMR

AF:

0.612

Gnomad ASJ

AF:

0.686

Gnomad EAS

AF:

0.481

Gnomad SAS

AF:

0.699

Gnomad FIN

AF:

0.705

Gnomad MID

AF:

0.655

Gnomad NFE

AF:

0.739

Gnomad OTH

AF:

0.658

GnomAD3 exomes

AF:

0.669

AC:

168073

AN:

251288

Hom.:

57461

AF XY:

0.678

AC XY:

92137

AN XY:

135816

show subpopulations

Gnomad AFR exome

AF:

0.633

Gnomad AMR exome

AF:

0.513

Gnomad ASJ exome

AF:

0.692

Gnomad EAS exome

AF:

0.468

Gnomad SAS exome

AF:

0.705

Gnomad FIN exome

AF:

0.702

Gnomad NFE exome

AF:

0.734

Gnomad OTH exome

AF:

0.693

GnomAD4 exome

AF:

0.717

AC:

1044840

AN:

1457796

Hom.:

377446

Cov.:

AF XY:

0.718

AC XY:

520797

AN XY:

725564

show subpopulations

Gnomad4 AFR exome

AF:

0.637

Gnomad4 AMR exome

AF:

0.530

Gnomad4 ASJ exome

AF:

0.693

Gnomad4 EAS exome

AF:

0.467

Gnomad4 SAS exome

AF:

0.706

Gnomad4 FIN exome

AF:

0.699

Gnomad4 NFE exome

AF:

0.738

Gnomad4 OTH exome

AF:

0.706

GnomAD4 genome

AF:

0.684

AC:

104107

AN:

152148

Hom.:

35975

Cov.:

AF XY:

0.680

AC XY:

50559

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.641

Gnomad4 AMR

AF:

0.612

Gnomad4 ASJ

AF:

0.686

Gnomad4 EAS

AF:

0.481

Gnomad4 SAS

AF:

0.698

Gnomad4 FIN

AF:

0.705

Gnomad4 NFE

AF:

0.739

Gnomad4 OTH

AF:

0.654

Alfa

AF:

0.720

Hom.:

10424

Bravo

AF:

0.671

Asia WGS

AF:

0.577

AC:

2007

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 16, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Autosomal recessive Robinow syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Nov 07, 2021

- -

Brachydactyly type B1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Nov 07, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.66

DANN

Benign

0.80

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over