9-91723417-T-C

Position:

chr9-91723417-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_004560.4(ROR2):c.*245A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0026 in 576,984 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0072 ( 14 hom., cov: 32)

Exomes 𝑓: 0.00094 ( 2 hom. )

Consequence

ROR2
NM_004560.4 3_prime_UTR

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -4.04

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:

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=-0.9).

BP6

Variant 9-91723417-T-C is Benign according to our data. Variant chr9-91723417-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 367490.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0072 (1097/152282) while in subpopulation AFR AF= 0.0252 (1045/41542). AF 95% confidence interval is 0.0239. There are 14 homozygotes in gnomad4. There are 502 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 14 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ROR2	NM_004560.4 linkuse as main transcript	c.*245A>G		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.*245A>G	3_prime_UTR_variant	9/9	1	NM_004560.4	ENSP00000364860	P1
ROR2	ENST00000375715.5 linkuse as main transcript	c.1920+737A>G	intron_variant		1		ENSP00000364867
ROR2	ENST00000550066.5 linkuse as main transcript	n.3545A>G	non_coding_transcript_exon_variant	11/11	2

Frequencies

GnomAD3 genomes

AF:

0.00717

AC:

1091

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0251

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00281

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00239

GnomAD4 exome

AF:

0.000944

AC:

401

AN:

424702

Hom.:

Cov.:

AF XY:

0.000797

AC XY:

177

AN XY:

221980

show subpopulations

Gnomad4 AFR exome

AF:

0.0257

Gnomad4 AMR exome

AF:

0.00199

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000481

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000389

Gnomad4 OTH exome

AF:

0.00182

GnomAD4 genome

AF:

0.00720

AC:

1097

AN:

152282

Hom.:

Cov.:

AF XY:

0.00674

AC XY:

502

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.0252

Gnomad4 AMR

AF:

0.00281

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00543

Hom.:

Bravo

AF:

0.00833

Asia WGS

AF:

0.00231

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Autosomal recessive Robinow syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Brachydactyly type B1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 28, 2021

See Variant Classification Assertion Criteria. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.075

DANN

Benign

0.54

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