GeneBe

rs1284777873

Variant names:

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP3

The NM_002958.4(RYK):​c.77_85delCGCCGCCGC​(p.Pro26_Pro28del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000674 in 148,414 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000067 ( 0 hom., cov: 30)

Consequence

RYK
NM_002958.4 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.31
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP3
Nonframeshift variant in repetitive region in NM_002958.4

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RYKNM_002958.4 linkc.77_85delCGCCGCCGC p.Pro26_Pro28del disruptive_inframe_deletion Exon 1 of 15 ENST00000623711.4 NP_002949.2 P34925-1Q59FQ5Q8WTZ8
RYKNM_001005861.3 linkc.77_85delCGCCGCCGC p.Pro26_Pro28del disruptive_inframe_deletion Exon 1 of 15 NP_001005861.1 P34925-2Q59FQ5Q8WTZ8
RYKXR_007095716.1 linkn.282_290delCGCCGCCGC non_coding_transcript_exon_variant Exon 1 of 12

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RYKENST00000623711.4 linkc.77_85delCGCCGCCGC p.Pro26_Pro28del disruptive_inframe_deletion Exon 1 of 15 1 NM_002958.4 ENSP00000485095.1 P34925-1
RYKENST00000620660.4 linkc.77_85delCGCCGCCGC p.Pro26_Pro28del disruptive_inframe_deletion Exon 1 of 15 1 ENSP00000478721.1 P34925-2

Frequencies

GnomAD3 genomes
AF:
0.00000674
AC:
1
AN:
148414
Hom.:
0
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.0000150
Gnomad OTH
AF:
0.00
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.00000674
AC:
1
AN:
148414
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
72302
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000150
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1284777873; hg19: chr3-133969413; API