Genetic Variant RYK:p.Pro27_Pro28dup (chr3-134250569-A-AGCGGCG) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP3BP6_ModerateBA1

The NM_002958.4(RYK):c.80_85dupCGCCGC(p.Pro27_Pro28dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00306 in 1,078,532 control chromosomes in the GnomAD database, including 65 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.017 ( 45 hom., cov: 30)

Exomes 𝑓: 0.00085 ( 20 hom. )

Consequence

RYK
NM_002958.4 conservative_inframe_insertion

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 1.28

Publications

0 publications found

Variant links:

Genes affected

RYK (HGNC:10481): (receptor like tyrosine kinase) The protein encoded by this gene is an atypical member of the family of growth factor receptor protein tyrosine kinases, differing from other members at a number of conserved residues in the activation and nucleotide binding domains. This gene product belongs to a subfamily whose members do not appear to be regulated by phosphorylation in the activation segment. It has been suggested that mediation of biological activity by recruitment of a signaling-competent auxiliary protein may occur through an as yet uncharacterized mechanism. The encoded protein has a leucine-rich extracellular domain with a WIF-type Wnt binding region, a single transmembrane domain, and an intracellular tyrosine kinase domain. This protein is involved in stimulating Wnt signaling pathways such as the regulation of axon pathfinding. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Feb 2012]

RYK links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_002958.4

BP6

Variant 3-134250569-A-AGCGGCG is Benign according to our data. Variant chr3-134250569-A-AGCGGCG is described in ClinVar as Benign. ClinVar VariationId is 780896.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0565 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002958.4. 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
	RYK	NM_002958.4	MANE Select	c.80_85dupCGCCGC	p.Pro27_Pro28dup	conservative_inframe_insertion	Exon 1 of 15	NP_002949.2	P34925-1
	RYK	NM_001005861.3		c.80_85dupCGCCGC	p.Pro27_Pro28dup	conservative_inframe_insertion	Exon 1 of 15	NP_001005861.1	P34925-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RYK	ENST00000623711.4	TSL:1 MANE Select	c.80_85dupCGCCGC	p.Pro27_Pro28dup	conservative_inframe_insertion	Exon 1 of 15	ENSP00000485095.1	P34925-1
RYK	ENST00000620660.4	TSL:1	c.80_85dupCGCCGC	p.Pro27_Pro28dup	conservative_inframe_insertion	Exon 1 of 15	ENSP00000478721.1	P34925-2
RYK	ENST00000946535.1		c.80_85dupCGCCGC	p.Pro27_Pro28dup	conservative_inframe_insertion	Exon 1 of 16	ENSP00000616594.1

Frequencies

GnomAD3 genomes

AF:

0.0169

AC:

2506

AN:

148398

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0585

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00528

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000195

Gnomad SAS

AF:

0.000209

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000165

Gnomad OTH

AF:

0.0107

GnomAD4 exome

AF:

0.000846

AC:

787

AN:

930026

Hom.:

Cov.:

AF XY:

0.000779

AC XY:

343

AN XY:

440558

show subpopulations

African (AFR)

AF:

0.0347

AC:

630

AN:

18168

American (AMR)

AF:

0.00198

AC:

AN:

6072

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

10796

East Asian (EAS)

AF:

0.00

AC:

AN:

21082

South Asian (SAS)

AF:

0.0000576

AC:

AN:

17362

European-Finnish (FIN)

AF:

0.00

AC:

AN:

17810

Middle Eastern (MID)

AF:

0.000414

AC:

AN:

2414

European-Non Finnish (NFE)

AF:

0.0000899

AC:

AN:

800528

Other (OTH)

AF:

0.00198

AC:

AN:

35794

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.455

Heterozygous variant carriers

122

152

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

112

140

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0169

AC:

2511

AN:

148506

Hom.:

Cov.:

AF XY:

0.0164

AC XY:

1184

AN XY:

72412

show subpopulations

African (AFR)

AF:

0.0585

AC:

2397

AN:

40978

American (AMR)

AF:

0.00527

AC:

AN:

14990

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3422

East Asian (EAS)

AF:

0.000196

AC:

AN:

5108

South Asian (SAS)

AF:

0.000209

AC:

AN:

4792

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9218

Middle Eastern (MID)

AF:

0.00

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.000165

AC:

AN:

66726

Other (OTH)

AF:

0.0106

AC:

AN:

2070

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

111

222

333

444

555

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

150

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

RYK-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.3

Mutation Taster

=300/0

polymorphism

(source)

Splicing

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over