Variant 9-91723486-GCTCT-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

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

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.383

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:

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ACMG classification

Classification made for transcript

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	Protein	UniProt
ROR2	NM_004560.4 linkuse as main transcript	c.172_175del		3_prime_UTR_variant	9/9	ENST00000375708.4	NP_004551.2

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris
ROR2	ENST00000375708.4 linkuse as main transcript	c.172_175del	3_prime_UTR_variant	9/9	1	NM_004560.4	ENSP00000364860	P1
ROR2	ENST00000375715.5 linkuse as main transcript	c.1920+664_1920+667del	intron_variant		1		ENSP00000364867
ROR2	ENST00000550066.5 linkuse as main transcript	n.3472_3475del	non_coding_transcript_exon_variant	11/11	2

Frequencies

GnomAD3 genomes

AF:

0.411

AC:

62253

AN:

151520

Hom.:

12962

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.410

AC XY:

30393

AN XY:

74080

show subpopulations

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

LINK: link

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

Name

Calibrated prediction

Score

Prediction

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