9-91734760-C-T

Variant names:

• chr9-91734760-C-T
• rs7869182
• NM_004560.4:c.623-1324G>A

Variant summary

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

The NM_004560.4(ROR2):​c.623-1324G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.503 in 151,942 control chromosomes in the GnomAD database, including 19,523 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 0.50 (19523 hom., cov: 32)
• Consequence: ROR2 NM_004560.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.43
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.544 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ROR2	NM_004560.4	c.623-1324G>A		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.623-1324G>A		intron_variant	Intron 5 of 8	1	NM_004560.4	ENSP00000364860.3
ROR2	ENST00000375715.5	c.203-1324G>A		intron_variant	Intron 5 of 12	1		ENSP00000364867.1
ROR2	ENST00000550066.5	n.1091-1324G>A		intron_variant	Intron 7 of 10	2

Frequencies

GnomAD3 genomes AF: 0.503 AC: 76421 AN: 151824 Hom.: 19521 Cov.: 32

Gnomad AFR AF: 0.437

Gnomad AMI AF: 0.492

Gnomad AMR AF: 0.481

Gnomad ASJ AF: 0.556

Gnomad EAS AF: 0.461

Gnomad SAS AF: 0.407

Gnomad FIN AF: 0.557

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.549

Gnomad OTH AF: 0.495

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

GnomAD4 genome AF: 0.503 AC: 76439 AN: 151942 Hom.: 19523 Cov.: 32 AF XY: 0.501 AC XY: 37179 AN XY: 74252

African (AFR) AF: 0.436 AC: 18069 AN: 41436

American (AMR) AF: 0.481 AC: 7354 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.556 AC: 1927 AN: 3466

East Asian (EAS) AF: 0.461 AC: 2370 AN: 5142

South Asian (SAS) AF: 0.406 AC: 1956 AN: 4820

European-Finnish (FIN) AF: 0.557 AC: 5872 AN: 10548

Middle Eastern (MID) AF: 0.415 AC: 122 AN: 294

European-Non Finnish (NFE) AF: 0.549 AC: 37288 AN: 67942

Other (OTH) AF: 0.491 AC: 1033 AN: 2106

Alfa AF: 0.399 Hom.: 1191

Bravo AF: 0.496

Asia WGS AF: 0.402 AC: 1395 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.64
DANN	Benign	0.53
PhyloP100		-1.4
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: rs7869182; hg19: chr9-94497042;