rs4467996

Positions:

• chr9-91755433-C-A
• chr9-91755433-C-G
• chr9-91755433-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004560.4(ROR2):​c.494+638G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.629 in 152,192 control chromosomes in the GnomAD database, including 30,399 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 0.63 (30399 hom., cov: 34)
• Consequence: ROR2 NM_004560.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.546

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]

ACMG classification

Verdict is Benign. Variant got -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 = 0.705 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ROR2	NM_004560.4	c.494+638G>T		intron_variant		ENST00000375708.4	NP_004551.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ROR2	ENST00000375708.4	c.494+638G>T		intron_variant		1	NM_004560.4	ENSP00000364860	P1
ROR2	ENST00000375715.5	c.74+638G>T		intron_variant		1		ENSP00000364867
ROR2	ENST00000550066.5	n.962+638G>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.629 AC: 95655 AN: 152074 Hom.: 30363 Cov.: 34

Gnomad AFR AF: 0.712

Gnomad AMI AF: 0.526

Gnomad AMR AF: 0.661

Gnomad ASJ AF: 0.554

Gnomad EAS AF: 0.613

Gnomad SAS AF: 0.510

Gnomad FIN AF: 0.633

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.587

Gnomad OTH AF: 0.610

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

GnomAD4 genome AF: 0.629 AC: 95747 AN: 152192 Hom.: 30399 Cov.: 34 AF XY: 0.629 AC XY: 46810 AN XY: 74402

Gnomad4 AFR AF: 0.712

Gnomad4 AMR AF: 0.661

Gnomad4 ASJ AF: 0.554

Gnomad4 EAS AF: 0.612

Gnomad4 SAS AF: 0.510

Gnomad4 FIN AF: 0.633

Gnomad4 NFE AF: 0.587

Gnomad4 OTH AF: 0.610

Alfa AF: 0.585 Hom.: 32347

Bravo AF: 0.636

Asia WGS AF: 0.554 AC: 1924 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	1.1
DANN	Benign	0.40

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

Other links and lift over

dbSNP: rs4467996; hg19: chr9-94517715;