9-91732723-C-T

Variant names:

• chr9-91732723-C-T
• rs10992072
• NM_004560.4:c.937+399G>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.937+399G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 152,212 control chromosomes in the GnomAD database, including 2,203 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 0.16 (2203 hom., cov: 32)
• Consequence: ROR2 NM_004560.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.437
• 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.191 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ROR2	NM_004560.4	c.937+399G>A		intron_variant	Intron 6 of 8	ENST00000375708.4	NP_004551.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ROR2	ENST00000375708.4	c.937+399G>A		intron_variant	Intron 6 of 8	1	NM_004560.4	ENSP00000364860.3
ROR2	ENST00000375715.5	c.517+399G>A		intron_variant	Intron 6 of 12	1		ENSP00000364867.1
ROR2	ENST00000550066.5	n.1405+399G>A		intron_variant	Intron 8 of 10	2

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24547 AN: 152092 Hom.: 2203 Cov.: 32

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.0625

Gnomad AMR AF: 0.148

Gnomad ASJ AF: 0.182

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.0489

Gnomad FIN AF: 0.117

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.194

Gnomad OTH AF: 0.185

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

GnomAD4 genome AF: 0.161 AC: 24557 AN: 152212 Hom.: 2203 Cov.: 32 AF XY: 0.154 AC XY: 11426 AN XY: 74424

African (AFR) AF: 0.156 AC: 6494 AN: 41534

American (AMR) AF: 0.148 AC: 2257 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.182 AC: 631 AN: 3466

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5176

South Asian (SAS) AF: 0.0486 AC: 234 AN: 4818

European-Finnish (FIN) AF: 0.117 AC: 1238 AN: 10596

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.194 AC: 13183 AN: 68002

Other (OTH) AF: 0.183 AC: 387 AN: 2116

Alfa AF: 0.159 Hom.: 906

Bravo AF: 0.165

Asia WGS AF: 0.0350 AC: 122 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.064
DANN	Benign	0.50
PhyloP100		-0.44
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: rs10992072; hg19: chr9-94495005;