chr9-91723482-G-A

Variant names:

• chr9-91723482-G-A
• rs542396423
• NM_004560.4:c.*180C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004560.4(ROR2):​c.*180C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000518 in 965,920 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000024 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000024 (0 hom.)
• Consequence: ROR2 NM_004560.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.455
• Publications: 0 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), PanelApp Australia
• autosomal recessive Robinow syndrome

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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004560.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ROR2	NM_004560.4	MANE Select	c.*180C>T		3_prime_UTR	Exon 9 of 9	NP_004551.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ROR2	ENST00000375708.4	TSL:1 MANE Select	c.*180C>T		3_prime_UTR	Exon 9 of 9	ENSP00000364860.3	Q01974
	ROR2	ENST00000375715.5	TSL:1	c.1920+672C>T		intron	N/A	ENSP00000364867.1	B1APY4
	ROR2	ENST00000964760.1		c.*180C>T		3_prime_UTR	Exon 9 of 9	ENSP00000634819.1

Frequencies

GnomAD3 genomes AF: 0.0000242 AC: 3 AN: 124222 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000839

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000238 AC: 2 AN: 841580 Hom.: 0 Cov.: 11 AF XY: 0.00000235 AC XY: 1 AN XY: 425836

African (AFR) AF: 0.0000985 AC: 2 AN: 20306

American (AMR) AF: 0.00 AC: 0 AN: 23786

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16398

East Asian (EAS) AF: 0.00 AC: 0 AN: 34842

South Asian (SAS) AF: 0.00 AC: 0 AN: 56880

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32656

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2754

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 614828

Other (OTH) AF: 0.00 AC: 0 AN: 39130

GnomAD4 genome AF: 0.0000241 AC: 3 AN: 124340 Hom.: 0 Cov.: 31 AF XY: 0.0000495 AC XY: 3 AN XY: 60628

African (AFR) AF: 0.0000836 AC: 3 AN: 35866

American (AMR) AF: 0.00 AC: 0 AN: 11384

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2980

East Asian (EAS) AF: 0.00 AC: 0 AN: 4114

South Asian (SAS) AF: 0.00 AC: 0 AN: 4234

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8350

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 268

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 54646

Other (OTH) AF: 0.00 AC: 0 AN: 1752

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.20
DANN	Benign	0.69
PhyloP100		-0.46

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: rs542396423; hg19: chr9-94485764;