Genetic Variant ROR1:p.Arg5His (chr1-63774431-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005012.4(ROR1):c.14G>A(p.Arg5His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R5L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ROR1
NM_005012.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.74

Publications

0 publications found

Variant links:

Genes affected

ROR1 (HGNC:10256): (receptor tyrosine kinase like orphan receptor 1) This gene encodes a receptor tyrosine kinase-like orphan receptor that modulates neurite growth in the central nervous system. The encoded protein is a glycosylated type I membrane protein that belongs to the ROR subfamily of cell surface receptors. It is a pseudokinase that lacks catalytic activity and may interact with the non-canonical Wnt signalling pathway. This gene is highly expressed during early embryonic development but expressed at very low levels in adult tissues. Increased expression of this gene is associated with B-cell chronic lymphocytic leukaemia. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jun 2012]

ROR1 Gene-Disease associations (from GenCC):

hearing loss, autosomal recessive 108
Inheritance: Unknown, AR Classification: MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, PanelApp Australia
hearing loss, autosomal recessive
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
nonsyndromic genetic hearing loss
Inheritance: AR Classification: LIMITED Submitted by: ClinGen

ROR1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.22362924).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005012.4. 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
	ROR1	NM_005012.4	MANE Select	c.14G>A	p.Arg5His	missense	Exon 1 of 9	NP_005003.2
	ROR1	NM_001083592.2		c.14G>A	p.Arg5His	missense	Exon 1 of 7	NP_001077061.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ROR1	ENST00000371079.6	TSL:1 MANE Select	c.14G>A	p.Arg5His	missense	Exon 1 of 9	ENSP00000360120.1
	ROR1	ENST00000371080.5	TSL:1	c.14G>A	p.Arg5His	missense	Exon 1 of 7	ENSP00000360121.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1027358

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

489592

African (AFR)

AF:

0.00

AC:

AN:

20466

American (AMR)

AF:

0.00

AC:

AN:

6126

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

11064

East Asian (EAS)

AF:

0.00

AC:

AN:

19394

South Asian (SAS)

AF:

0.00

AC:

AN:

20532

European-Finnish (FIN)

AF:

0.00

AC:

AN:

17296

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2568

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

890928

Other (OTH)

AF:

0.00

AC:

AN:

38984

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.38

BayesDel_addAF

Benign

-0.019

BayesDel_noAF

Benign

-0.27

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.077

Eigen

Benign

-0.43

Eigen_PC

Benign

-0.27

FATHMM_MKL

Benign

0.30

LIST_S2

Benign

0.57

M_CAP

Pathogenic

0.76

MetaRNN

Benign

0.22

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.0

PhyloP100

1.7

PrimateAI

Pathogenic

0.92

PROVEAN

Benign

-0.12

REVEL

Benign

0.13

Sift

Benign

0.21

Sift4G

Benign

0.18

Polyphen

0.0

Vest4

0.17

MutPred

0.19

Loss of methylation at R5 (P = 0.0121)

MVP

0.76

MPC

0.54

ClinPred

0.28

GERP RS

3.2

PromoterAI

-0.065

Neutral

(source)

Varity_R

0.057

gMVP

0.49

Mutation Taster

=85/15

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over