chr9-91857995-A-T

Variant names:

• chr9-91857995-A-T
• rs12376130
• NM_004560.4:c.98-82177T>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.98-82177T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.341 in 152,090 control chromosomes in the GnomAD database, including 9,183 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 0.34 (9183 hom., cov: 32)
• Consequence: ROR2 NM_004560.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.731
• Publications: 3 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

LOC124902210 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.472 is higher than 0.05.

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.98-82177T>A		intron	N/A	NP_004551.2
	ROR2	NM_001318204.2		c.98-82177T>A		intron	N/A	NP_001305133.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ROR2	ENST00000375708.4	TSL:1 MANE Select	c.98-82177T>A		intron	N/A	ENSP00000364860.3	Q01974
	ROR2	ENST00000375715.5	TSL:1	c.-323-82177T>A		intron	N/A	ENSP00000364867.1	B1APY4
	ROR2	ENST00000964760.1		c.98-82177T>A		intron	N/A	ENSP00000634819.1

Frequencies

GnomAD3 genomes AF: 0.341 AC: 51761 AN: 151972 Hom.: 9146 Cov.: 32

Gnomad AFR AF: 0.355

Gnomad AMI AF: 0.288

Gnomad AMR AF: 0.482

Gnomad ASJ AF: 0.272

Gnomad EAS AF: 0.475

Gnomad SAS AF: 0.303

Gnomad FIN AF: 0.334

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.297

Gnomad OTH AF: 0.348

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

GnomAD4 genome AF: 0.341 AC: 51839 AN: 152090 Hom.: 9183 Cov.: 32 AF XY: 0.344 AC XY: 25585 AN XY: 74314

African (AFR) AF: 0.356 AC: 14761 AN: 41478

American (AMR) AF: 0.482 AC: 7361 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.272 AC: 946 AN: 3472

East Asian (EAS) AF: 0.476 AC: 2464 AN: 5180

South Asian (SAS) AF: 0.303 AC: 1453 AN: 4798

European-Finnish (FIN) AF: 0.334 AC: 3540 AN: 10592

Middle Eastern (MID) AF: 0.333 AC: 98 AN: 294

European-Non Finnish (NFE) AF: 0.297 AC: 20211 AN: 67974

Other (OTH) AF: 0.352 AC: 742 AN: 2108

Alfa AF: 0.325 Hom.: 1039

Bravo AF: 0.355

Asia WGS AF: 0.411 AC: 1433 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	8.8
DANN	Benign	0.88
PhyloP100		0.73
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: rs12376130; hg19: chr9-94620277;