NM_004560.4:c.623-1962T>G

Variant names:

• chr9-91735398-A-C
• rs4237215
• NM_004560.4:c.623-1962T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004560.4(ROR2):​c.623-1962T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.657 in 151,972 control chromosomes in the GnomAD database, including 33,034 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.66 (33034 hom., cov: 31)
• Consequence: ROR2 NM_004560.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.476
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• brachydactyly type B1

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• autosomal recessive Robinow syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.728 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ROR2	NM_004560.4	c.623-1962T>G		intron_variant	Intron 5 of 8	ENST00000375708.4	NP_004551.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ROR2	ENST00000375708.4	c.623-1962T>G		intron_variant	Intron 5 of 8	1	NM_004560.4	ENSP00000364860.3
ROR2	ENST00000375715.5	c.203-1962T>G		intron_variant	Intron 5 of 12	1		ENSP00000364867.1
ROR2	ENST00000550066.5	n.1091-1962T>G		intron_variant	Intron 7 of 10	2

Frequencies

GnomAD3 genomes AF: 0.657 AC: 99752 AN: 151854 Hom.: 33006 Cov.: 31

Gnomad AFR AF: 0.734

Gnomad AMI AF: 0.695

Gnomad AMR AF: 0.573

Gnomad ASJ AF: 0.661

Gnomad EAS AF: 0.514

Gnomad SAS AF: 0.671

Gnomad FIN AF: 0.613

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.646

Gnomad OTH AF: 0.621

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.657 AC: 99832 AN: 151972 Hom.: 33034 Cov.: 31 AF XY: 0.653 AC XY: 48521 AN XY: 74268

African (AFR) AF: 0.735 AC: 30425 AN: 41422

American (AMR) AF: 0.573 AC: 8748 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.661 AC: 2289 AN: 3464

East Asian (EAS) AF: 0.514 AC: 2648 AN: 5154

South Asian (SAS) AF: 0.670 AC: 3226 AN: 4816

European-Finnish (FIN) AF: 0.613 AC: 6463 AN: 10546

Middle Eastern (MID) AF: 0.544 AC: 160 AN: 294

European-Non Finnish (NFE) AF: 0.646 AC: 43941 AN: 67996

Other (OTH) AF: 0.616 AC: 1298 AN: 2106

Alfa AF: 0.640 Hom.: 50177

Bravo AF: 0.653

Asia WGS AF: 0.588 AC: 2043 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	4.9
DANN	Benign	0.84
PhyloP100		-0.48
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4237215; hg19: chr9-94497680;